3 Year Index

T ECHNOLOGY, PRODUCTS, MA RKETS AND SERVICE OPPORTUNITIES

A NEW MEDICINE PUBLICATION VOLUME 3, NUMBER 1-12 INDEX MAY 1998

TABLE OF CONTENTS

Ingenex 584 HEAD AND NECK CANCER — PART II STATE-OF-THE-ART IN THE MANAGEMENT OF CANCER IMMUNOTHERAPY/VACCINES 584 DIAGNOSIS, STAGING, PROGNOSIS, OVARIAN CANCER — PART III AltaRex 584 AND TREATMENT CURRENT TREATMENT APPROACHES AVAX Technologies 585 DIAGNOSIS, SCREENING AND STAGING 626 Biomira 585 Panendoscopy 626 CYTOREDUCTIVE SURGERY 545 Corixa 586 Non-invasive Imaging 627 Second Look Surgery 546 Trilex Pharmaceuticals 586 In vitro Tests 627 Prophylactic Oophorectomy 547 Other 586 Human papillomavirus (HPV) 627 RADIATION THERAPY 548 SMALL MOLECULE DRUGS 586 Epstein-Barr virus 628 CHEMOTHERAPY 548 CDR Therapeutics 586 Telomerase 628 Primary Disease 549 Sugen 587 Cytology 629 Single-agent chemotherapy 549 RADIOISOTOPES/RADIOIMMUNOCONJUGATES 587 Biological Staging 629 Combination chemotherapy 549 Cancer Therapeutics 587 PROGNOSIS 629 Drug Resistance 551 Immunomedics 588 p53 629 Recurrent/Refractory Disease 551 NeoRx 588 Growth Factors 631 High-Dose (Density) Chemotherapy with Autologous Bone Marrow and/ University of Alabama 588 Cyclin D1 631 or Stem Cell Transplants 557 University of Chicago 589 Eukaryotic Initiation Factor 4E 631 Drug Administration Routes 561 PHOTODYNAMIC THERAPY 589 HPV Infection 631 INHIBITION OF METASTASIS 589 Multiple Markers 631 OVARIAN CANCER — PART IV Anika Therapeutics 589 TREATMENT OPTIONS BY SITE OF CANCER 632 NOVEL THERAPEUTIC APPROACHES MOLECULAR APPROACHES TO Oral Cavity and Oropharynx 633 IN DEVELOPMENT MANAGEMENT OF OVARIAN CANCER 589 Nasopharynx and Hypopharynx 633 BRCA1/BRCA2 590 ANALOGS, DERIVATIVES AND FORMULATIONS Second Primary Tumors 633 OF AGENTS APPROVED FOR THE TREATMENT p53 590 MULTIMODALITY THERAPY 633 OF OVARIAN AND OTHER CANCERS 570 ras 590 Anthracyclines 570 Cortecs International 590 HEAD AND NECK CANCER — PART III Anthra Pharmaceuticals 570 Her-2/neu (erbB-2) 590 NOVEL THERAPEUTIC AND Platinum Analogs 571 Anti-erbB-2 sFv (Ad21) 590 CHEMOPREVENTIVE APPROACHES Oxaliplatin 571 Epidermal Growth Factor Receptor IN DEVELOPMENT (EGFr) 590 Taxanes 571 RADIATION THERAPY 646 Paclitaxel 571 RADIOSENSITIZATION/ENHANCEMENT 646 Docetaxel 581 HEAD AND NECK CANCER — PART I Pharmacyclics 647 Topoisomerase I Inhibitors 581 EPIDEMIOLOGY, ETIOLOGY AND Enzon 647 GW211 581 MOLECULAR MARKERS Vion Pharmaceuticals 648 Gemcitabine 581 EPIDEMIOLOGY 606 PHOTODYNAMIC THERAPY 648 DRUG RESISTANCE 581 International Epidemiology 606 QLT PhotoTherapeutics 648 Methionine 581 USA Epidemiology 606 Scotia 648 AntiCancer 581 ETIOLOGY AND RISK FACTORS 607 COMMERCIALLY AVAILABLE AGENTS IN Molecular Markers 582 Oral Cancer 608 CLINICAL TRIALS IN HNSCC 650 Resistance to Platinum-based/ Nasopharyngeal Cancer 610 Gemcitabine 650 Alkylating Agents 582 MOLECULAR MARKERS 610 Vinorelbine 650 Intracellular glutathione 583 Oncogenes and Tumor Taxanes 650 Metallothioneins 583 Suppressor Genes 610 NOVEL CHEMOTHERAPEUTICS 650 Resistance to Taxanes 583 Growth Factors 611 Thymidylate Synthase Inhibitors 650 SDZ PSC 833 583 Matrix Metalloproteinases 612 Retinoids 650 Chemoprotection 584 Other Molecular Factors 613 ALRT1550 650 Genetix Pharmaceuticals 584 MOLECULAR EPIDEMIOLOGY 613 GENE THERAPY 651

p53 651 Scintigraphy 683 UPDATE OF PROSTATE CANCER — Introgen Therapeutics 651 In Vitro Tests 683 PART I Schering-Plough Research Institute 651 TUMOR STAGING 683 EPIDEMIOLOGY p16 651 PROGNOSIS 684 USA Epidemiology 731 Suicide Genes 651 Onyx-015 654 CANCER OF THE CENTRAL CANCER OF THE CENTRAL Human Papillomavirus (HPV) 654 NERVOUS SYSTEM — PART II NERVOUS SYSTEM — PART III GROWTH FACTORS/CYTOKINES 654 CURRENT THERAPEUTIC NOVEL THERAPEUTIC APPROACHES APPROACHES Epidermal Growth Factor (EGF) NOVEL CHEMOTHERAPEUTICS 731 Receptor Inhibitors 654 SURGERY 702 9-aminocamptothecin (9-AC) 731 Quinazolines 654 Conventional Surgery 702 Alanosine 731 MDX-447 655 Stereotaxic Radiosurgery 702 Diaziquone 733 MAb ICR62 655 RADIOTHERAPY 703 Dibromodulcitol (DBD) 733 Interferon as Adjuvant Therapy 655 Conventional Radiation Therapy 703 Fluorodeoxyuridine (FdUrd) 734 Tumor Necrosis Factor α (TNF-α) 655 Interstitial Radiation or Brachytherapy 703 Hypericin 734 IMMUNOTHERAPY/VACCINES 655 Mivobulin Isethionate 734 Cel-Sci 655 International Isotopes 705 O(6)-benzylguanine 734 GeneMedicine 656 Boron Neutron Capture Therapy (BNCT) 706 Phenylacetate 735 University of Pittsburgh 656 Boron Biologicals 706 Phenylbutyrate 735 MANAGEMENT OF TREATMENT-RELATED Radiosensitizers 707 Rebeccamycin Analog 735 COMPLICATIONS 656 Cisplatin or carboplatin 707 Suramin 735 Amifostene 656 Etanidazole 707 Temozolomide 736 Lisofylline 656 Gadolinium texaphyrin UCN-01 736 Oralease 656 (Gd-Tex) 707 RECEPTOR TARGETING STRATEGIES 737 DRUG DELIVERY 657 Halogenated pyrimidine CEP751 737 Genetronics 657 analogs 707 IL4 (38-37)-PE38KDEL 737 CHEMOPREVENTION 657 Neu-Sensamide 709 IL13-PE38QQR 738 Tirapazamine 709 2 SU101 738 CANCER OF THE CENTRAL NERVOUS HYPERTHERMIA 709 SYSTEM — PART I THERAPY ENHANCEMENT 738 PHOTODYNAMIC THERAPY 709 Radiosensitization 738 EPIDEMIOLOGY, ETIOLOGY, DIAGNOSIS Pacific Pharmaceuticals 709 AND PROGNOSIS RSR-13 738 CHEMOTHERAPY 710 Chemosensitization 738 WORLDWIDE EPIDEMIOLOGY OF Approved Drugs for CNS Cancer PRIMARY CNS TUMORS 670 Indications 710 Artificial oxygen carriers 738 USA Epidemiology 670 Carmustine and lomustine 710 Chemoprotection 739 Gender 670 Gliadel 710 Dexrazoxane 739 Race 670 Commercial Drugs in Clinical Trials NOVEL APPROACHES TO PREVENT/ Age 670 for CNS Cancer Indications 712 TREAT METASTASES 739 EPIDEMIOLOGY OF SECONDARY Chemotherapy Delivery Options 712 Matrix Metalloproteinase (MMP) CNS TUMORS 670 Intra-arterial chemotherapy 712 Inhibitors 739 EPIDEMIOLOGY OF METASTATIC Intrathecal chemotherapy 712 Bryostatin-1 739 CNS CANCER 672 DepoCyt 717 Marimastat 745 Neoplastic Meningitis 672 HEMATOPOIETIC SUPPORT/BONE MARROW Inhibition of Angiogenesis 746 ETIOLOGY OF PRIMARY TUMORS TRANSPLANTATION 718 Carboxyamide triaxole (CAI) 746 OF THE CNS 673 CURRENT TREATMENT BY TUMOR TYPE 723 MAb 81C6 746 Hereditary/Familial Factors 673 Primary Malignant CNS Cancer 723 Thalidomide 746 Environmental Factors 674 Pediatric Tumors 723 TNP-470 746 Other Factors 674 Metastatic Brain Tumors and Cancer Vascular endothelial growth factor MOLECULAR GENETICS AND MOLECULAR Metastisized to the Brain 724 (VEGF) 746 BIOLOGY OF PRIMARY BRAIN TUMORS 675 MANAGEMENT OF TREATMENT-RELATED Selective Targeting of Tumor Gene Factors 675 AND OTHER COMPLICATIONS 724 Vasculature 747 Chromosomal/gene abnormalities 675 Hearing Loss 724 Exploiting Other Mechanisms 747 Gene amplification 680 Peritumoral Brain Edema 724 Brain-enriched hyaluronan-binding Growth Factors 681 Shunts 725 protein (BEHAB) 747 DIAGNOSIS 681 Steroids 725 Glioma-specific Chloride Channel 747 Neuroimaging 682 Human corticotropin-releasing IMMUNOTHERAPY/VACCINES 747 Stereotactic Techniques for Tissue factor (hCRF) 725 Antigen-specific Cellular Sampling 683 Seizures 725 Immunotherapy 747

Activated Cytotoxic T Cells 747 Combination Therapies 620 Genetically-modified Tumor Cells 748 MEETING COVERAGE HEPATOCELLULAR CARCINOMA 621 Granulocyte-macrophage colony- ASCUS PATIENT MANAGEMENT Multimodality Therapy 621 stimulating factor (GM-CSF) 748 IN CERVICAL CANCER SCREENING Liver transplantation combined Immune Response 748 with neoadjuvant and adjuvant FROM THE 45TH ANNUAL CLINICAL MEETING chemotherapy 621 Anti-hCG Vaccines 748 OF THE AMERICAN COLLEGE OF OBSTETRICIANS Intra-arterial Lipodol-iodine 131 621 Administration of Growth AND GYNECOLOGISTS Factors/Cytokines 748 LAS VEGAS, NV, APRIL 28-30, 1997 PANCREATIC CANCER 621 PNU-214565 621 “SUICIDE” GENE THERAPY 749 SCREENING AND DIAGNOSIS OF Adenoviral Vector-mediated Transfer 749 CERVICAL CANCER 562 COLORECTAL CANCER 622 IntroGene 749 ROLE OF HUMAN PAPILLOMAVIRUS Monotherapy 622 University of Pennsylvania 749 IN CERVICAL CANCER 562 AG-337 622 Parvoviral Vector-mediated Transfer 749 Digene’s Hybrid Capture HPV Raltitrexed 622 DNA Assay 564 Avigen 749 Irinotecan 622 DIAGNOSTIC TRIAGE USING HPV Retroviral Vector-mediated Transfer 750 Capecitabine 622 SCREENING 564 Combination Regimens 623 Chiron 750 5-FU Administration Options 623 Genetic Therapy/Novartis 750 NEW DEVELOPMENTS IN THE Multimodality Therapy 623 MONOCLONAL ANTIBODIES 750 TREATMENT Chemoradiation 623 Lexigen Pharmaceuticals 750 OF GYNECOLOGIC CANCERS CARCINOID SYNDROME 623 Techniclone 751 FROM THE 21ST CONGRESS OF THE EUROPEAN Octreotide Acetate LAR 623 NOVEL POTENTIAL TREATMENTS DRIVEN SOCIETY OF MEDICAL ONCOLOGY IENNA USTRIA OVEMBER BY NEW GENE DISCOVERIES 751 V , A , N 1-5, 1996 NEW APPROACHES FOR THE DELIVERY OF THERAPEUTICS TO INVASIVE CERVICAL CANCER 565 TREATMENT OF HEAD AND NECK THE RAIN Metastatic Cervical Cancer 565 B 752 CANCER Electroporation for Delivery HIV-related invasive cervical of Genes 752 cancer 565 FROM THE 33RD ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY Combination Regimens in Invasive Crossing the Blood-Brain Barrier DENVER, CO, MAY 17-20, 1997 (BBB) 752 Cervical Cancer 565 MULTIMODALITY THERAPY 641 Cereport 752 BEMP regimen 565 3 Taxanes 641 SP2000 Biotransport 752 Docetaxel 641 DEMYSTIFYING THE ROLE OF Paclitaxel 641 PROSTATE CANCER — PART II CYTOKINES IN TUMOR IMMUNOBIOLOGY Thymidylate Synthase Inhibitors 642 DIAGNOSIS, STAGING, AG337 642 PROGNOSIS, SCREENING, REPORT FROM THE 88TH ANNUAL MEETING AND NOVEL MOLECULAR OF THE AMERICAN ASSOCIATION FOR CANCER RADIOSENSITIZATION 642 MARKERS RESEARCH APRIL 12-16, 1997 SAN DIEGO, CA Tirapazamine 642 CHEMOTHERAPY 642 DIAGNOSTIC AND SCREENING TESTS 762 MECHANISMS OF GENE REGULATION BY TUMOR NECROSIS FACTOR (TNF) 601 Vinorelbine 642 Prostate-specific Antigen (PSA) 762 FLT 3 LIGAND (FLT-3L) 601 GENE THERAPY 642 Prostate Acid Phosphatase (PAP) 764 IL-6 RECEPTOR SUPER-ANTAGONISTS Adp53 642 ProstaScint 764 (SANTS): NEW TOOLS FOR MULTIPLE EPIDERMAL GROWTH FACTOR Angiogenesis 764 MYELOMA 602 RECEPTOR ANTAGONIST 643 Cytokine Overexpression 765 CYTOKINES THAT PREVENT OR PROMOTE C225 643 NOVEL MOLECULAR MARKERS 765 TUMOR CELL DEATH 602 INTERFERON-α 643 Markers Associated with Familial/ EBV-associated Lymphoma 602 Induction 643 Hereditary Prostate Cancer 766 EBV-associated AIDS Primary CNS Biochemoprevention 643 Androgen receptor 766 Lymphomas (AIDS-PCNSL) 603 Natural Killer (NK) Cell Leukemias 603 BRCA1 or BRCA2 766 OPPORTUNISTIC INFECTIONS IN Hereditary prostate cancer 1 IMMUNOCOMPROMISED PATIENTS (HPCA1) 766 NEW APPROACHES IN THE FROM THE 37TH INTERSCIENCE CONFERENCE TREATMENT OF Other Markers 768 ON ANTIMICROBIAL AGENTS AND CHEMOTHERAPY GASTROINTESTINAL CANCERS Insulin-like growth factor-I (ICAAC), TORONTO, ONTARIO, CANADA, (IGF-I) 768 FROM THE 33RD ANNUAL MEETING OF THE SEPTEMBER 28-OCTOBER 1, 1997 AMERICAN SOCIETY OF CLINICAL ONCOLOGY Nuclear matrix proteins BACTERIAL INFECTIONS 657 DENVER, CO, MAY 17-20, 1997 (NMPs) 768 Risk Factors For Gram-Positive P53 769 GASTRIC CANCER 620 Infections 658 Prostate specific membrane Monotherapy 620 Capnacytophaga Bacteremia 658 antigen (PSMA) 769 Docetaxel 620 The Growing Problem of Prostate stem cell antigen (PSCA) 769 Paclitaxel 620 Vancomycin-Resistant Enterococci 658

Quinupristin/dalfopristin 659 Targeting Protease Production 685 Paraneoplastic Opsoclonus/ LY 333328 659 Peptidyl methyl ketone 685 Encephalopathy 727 Daptomycin 660 Marimastat 685 Progressive Multifocal Linezolid 660 Carboxy-amido-triazole (CAI) 685 Leukoencephalopathy 727 Ziracin 660 MECHANISMS OF DRUG-INDUCED Other agents 660 APOPTOSIS 685 ADVANCES IN THE MANAGEMENT OF Vancomycin-Intermediate TELOMERASE IN CANCERS OF THE GASTROINTESTINAL CANCER Staphylococcus aureus 660 NERVOUS SYSTEM 687 FROM THE 62ND ANNUAL SCIENTIFIC Methicillin-resistant HERPES VECTORS FOR BRAIN MEETING OF THE AMERICAN COLLEGE Staphylococcus aureus 660 TUMOR THERAPY 687 OF GASTROENTEROLOGY (ACG) CHICAGO, IL; NOVEMBER 3-5, 1997 Other Bacterial Infections in Basic HSV Gene Therapy Vector 693 Cancer Patients 660 Improved HSV Recombinant Vector 693 BARRETT’S ESOPHAGUS 753 Penicillin-resistant Streptococcus HSV-1 Amplicon 693 Prevalence of Short-Segment pneumoniae 660 Helper Virus-free Packaging System 694 Barrett’s Esophagus (SSBE) 753 Stenotrophomonas maltophilia 660 Diagnosis and Treatment of SSBE 753 FARNESYL TRANSFERASE INHIBITORS Pseudomonas aeruginosa 661 AND ANTI-RAS THERAPY 694 PREVENTION AND TREATMENT OF ESOPHAGEAL CANCER 753 FUNGAL INFECTIONS 661 TARGETING P53-DEFICIENT CELLS Candida Fungi 661 WITH ADENOVIRUS MUTANTS 695 Photodynamic Therapy 753 Zygomycosis 661 Barrett’s dysplasia 753 Fusarium 661 A REPORT ON MOLECULAR MEDICINE Refractory adenocarcinoma Antifungals in Development 662 OF CANCER, A GENETIC DISEASE of the distal esophagus 753 Beta-carotene 753 Nyotran 662 FROM THE NINTH ANNUAL USHA MAHAJANI Echinocandin derivatives 662 SYMPOSIUM AT THE SALK INSTITUTE, Stents 754 SCH 56592 662 SEPTEMBER 5, 1997 GASTRIC CANCER 754 Sordaricin derivatives 662 METHYLATION AND EPIGENETIC INSTABILITY Neoadjuvant Chemotherapy 754 IN THE DEVELOPMENT OF CANCER 696 Novel Antifungal R&D Programs 662 COLORECTAL CANCER 754 Imprinted Genes and RiboGene 662 Benefits of Screening 754 Childhood Tumors 696 Millennium Pharmaceuticals 663 Colon Cancer Prevention 754 Methylation of Normal Genes 696 Alpha-Beta Technology 663 Difluoromethylornithine (DFMO) 754 4 Hypermethylation 696 THERAPEUTIC APPROACHES FOR Aspirin 755 Mismatch repair genes 696 OPPORTUNISTIC INFECTIONS 663 Argon Plasma Coagulation of Bacterial Infections 663 Epimutations 697 Colorectal Adenomas 755 Cefepime 663 Loss of a protective mechanism 697 Ciprofloxacin 664 CHROMOSOMAL TRANSLOCATIONS ADVANCES IN THE MANAGEMENT OF IN CANCER 697 Viral Infections 664 HEMATOLOGIC MALIGNANCIES Bcl-2 697 Penciclovir 664 FROM THE 39TH ANNUAL MEETING OF THE Genes Involved in the Pre- AMERICAN SOCIETY OF HEMATOLOGY (ASH) Fungal Infections 665 initiation of Cancer 697 Liposomal amphotericin B 665 SAN DIEGO, CA; DECEMBER 5-9, 1997 EMERGING CYTOGENETIC TECHNOLOGIES ACUTE MYELOGENOUS LEUKEMIA (AML) 755 Aerosol amphotericin B TO DETECT QUANTITATIVE CHROMOSOME prophylaxis 665 CHANGES 698 Maxamine and IL-2 Combination Therapy 755 Fluconazole 665 BRCA1 AND BRCA2 GENES IN BREAST Granulocyte-macrophage colony AND OVARIAN CANCER 698 IL-2 Monotherapy 755 stimulating factor 666 Mutations Vary by Geography 698 ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) 756 Voriconazole 666 Actionable Cancer-propensity Genes 698 Shortened, Intensified Chemotherapy 756 Itraconazole oral solution 666 Sporadic Cancers 699 ACUTE PROMYELOCYTIC LEUKEMIA (APL) 756 Azole-based prophylaxis 666 Gene Therapy 699 New Spectrum of Opportunistic Concurrent Induction Chemotherapy Infections in Fludarabine- and All-trans Retinoic Acid (ATRA) 756 Treated CLL 666 NEW THERAPEUTIC APPROACHES IN NEURO-ONCOLOGY CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) 756 Fungal Pneumonia 667 Cladribine 756 FROM THE 49TH ANNUAL MEETING OF THE COSTS ASSOCIATED WITH ANTI-INFECTIVE CHRONIC MYELOGENOUS LEUKEMIA (CML) 756 AMERICAN ACADEMY OF NEUROLOGY THERAPY IN NEUTROPENIC PATIENTS 667 BOSTON, MA, APRIL 12-19, 1997 Decitabine 756 GLIOMAS 725 MYELODYSPLASTIC SYNDROME (MDS) 757 CANCER OF THE CENTRAL β Topotecan 757 NERVOUS SYSTEM Interferon -lA 725 Multimodality Regimens 726 Amifostine in Combination Therapy 757 FROM THE AMERICAN ASSOCIATION OF CANCER LYMPHOMAS 757 RESEARCH CONFERENCE High-dose Chemotherapy 726 JUNE 7-11, 1997, SAN DIEGO, CA CNS LYMPHOMAS 726 Poor Prognosis Malignant Lymphoma 757 TARGETING REGIONAL METASTASES PARANEOPLASTIC NEUROLOGICAL Non-Hodgkin’s Lymphoma (NHL) 758 OF BRAIN TUMORS 684 SYNDROMES 727 MULTIPLE MYELOMA 758

Interferon-α Maintenance 758 A series of phase I clinical trials Transcriptional Factors 598 Clarithromycin 758 adenoviral-based gene therapy for Chemoprotection 598 malignant mesothelioma with TREATMENT OF CHEMOTHERAPY-INDUCED Chemosensitization 598 concomitant immunosuppression 784 SIDE EFFECTS 758 UCN-01 598 Thrombocytopenia 758 Noninvasive imaging of adenoviral- mediated HSV-tk gene transfer and DRUG DEVELOPMENT AND RESEARCH Mucositis 759 expression 785 PROJECTS 599 Recombinant keratinocyte Other Prodrug Activating Small Molecule Drugs 599 growth factor 759 Gene Therapy 785 Mitotix 599 Mutant HSV-1 tk combined with Onyx 599 REPORT FROM THE SIXTH acyclovir (ACV) 785 ProScript 599 INTERNATIONAL CONFERENCE ON GENE THERAPY OF CANCER New enzyme/prodrug combinations Sugen 599 for use in gene-directed enzyme Peptide Mimetics 599 SPONSORED BY THE SIDNEY prodrug therapy (GDEPT)) 786 Cyclacel 599 KIMMEL CANCER CENTER THE BYSTANDER EFFECT 786 NOV 19-22, 1997, SAN DIEGO, CA Oligonucleotide-based Drugs 600 Evaluation of Adenovirus p53- Gilead Sciences 600 APOPTOSIS AND GENE THERAPY 770 mediated Bystander Effect In Vivo 786 Genomics 600 P53 772 Bystander Effect in HSV-Tk Suicide Ventana Genetics 600 Introgen Therapeutics 775 Gene Therapy 786 Other 600 Phase I clinical trials in head and IMPROVING DELIVERY APPROACHES 787 neck cancer 775 Icos 600 Enhancing Nonviral Delivery 787 Phase I studies of INGN 201 for Vaccinia Virus 787 treating non-small cell lung cancer 775 Tumor-specific Ligand-liposome Gene Ovarian cancer 776 ANTI-CANCER DRUG DEVELOPMENT Delivery 787 Preclinical studies of p53 replacement gene therapy TAXANES — PART I for pancreatic cancer 776 MECHANISMS IN MALIGNANCY STATUS OF TAXANES AND THE Tumor regression in vivo OUTLOOK FOR GENERIC VERSIONS OF PACLITAXEL following p53 combination THE CELL CYCLE therapy 776 CLINICAL ISSUES 614 CELL CYCLE CONTROL 591 Canji (Schering-Plough) 777 Taxol 615 Growth Signals 591 5 Phase I clinical trials of Taxotere 615 Cyclins and Cyclin-dependent intrahepatic SCH 58500 777 Paxene 615 Adenovirus-mediated p53 gene Kinases 591 TAXOL PATENT AND EXCLUSIVITY ISSUES 615 therapy synergizes with paclitaxel 777 Targets of cyclins and cdks 592 APPROVED/MARKETED GENERIC Onyx Pharmaceuticals 778 Mechanism of Action of the Retinoblastoma VERSIONS OF PACLITAXEL 616 Phase I clinical trial of ONYX-015 778 (Rb) Tumor Suppressor 592 Suppliers of Paclitaxel to Drug Preclinical studies with ONYX-015 Companies 616 in combination with chemotherapy 778 E2F regulation by cell cycle- dependent changes in subcellular Hauser 616 CELL CYCLE-BASED GENE THERAPY 779 localization 593 Indena 617 HepaVec 779 Molecular mechanisms of E2F NaPro BioTherapeutics 617 Canji 780 transcriptional regulation 593 Marketers of Generic Paclitaxel 619 BCL-2 780 Cyclins/cdk Regulation 594 Dabur 619 JNK/SAPK PATHWAY 781 CELL CYCLE DYSREGULATION AND CANCER 594 F. H. Faulding 619 Isis Pharmaceuticals 781 Cellular Response to Immunex 620 OTHER GENE THERAPY APPROACHES 781 Oncogenic Mutation 595 Yew Tree Pharmaceuticals 620 Inhibition of Nude Mice Xenografts p53 595 Using Growth Inhibitory Gene Mda-7 781 The role of p57 (Kip2) 595 TAXANES — PART II Anti-papillomavirus Ribozymes 782 Apoptosis 596 INDICATIONS, MARKETS, Anti-ras and Anti-raf Approaches 783 Viral Oncogenes 596 FORMULATIONS, ANALOGS AND Apoptin 783 DERIVATIVES, AND NOVEL SPINDLE DIAGNOSTIC/PROGNOSTIC APPLICATIONS Interleukin-1β Converting Enzyme POISONS OF CELL CYCLE 596 (ICE) 783 Cascade Oncogenics 596 CLINICAL STATUS 635 SUICIDE GENE THERAPY STRATEGIES 783 Ovarian Cancer 635 CELL CYCLE MODULATION AS AN Target Selectivity 783 ANTI-CANCER STRATEGY 597 Breast Cancer 635 Pre-emptive Suicide Gene Strategies 783 Direct Inhibitors of Cyclin:cdk 597 Kaposi’s Sarcoma 635 Herpes Simplex Virus Thymidine Flavopiridol 597 Lung Cancer 637 Kinase (HSV-tk) Gene Combined Combination Regimens 637 with the Prodrug Ganciclovir (GCV) 784 Olomoucine and roscovitine 598 TECHNICAL CHALLENGES 637 Phase II clinical trials of GLI 328 Inhibitors of Activation or Activators HSV-Tk gene therapy in recurrent of Inhibition of Cdk 598 Biomass Sources 637 glioblastoma 784 Activators of Cyclin:cdk Proteolysis 598 Formulations 637

Administration Routes 637 ChiRex 638 Phytogen Life Sciences 639 MARKET OPPORTUNITY 637 Gensia Sicor 638 Sparta Pharmaceuticals 639 PACLITAXEL EXTRACTS AND Phytogen Life Sciences 638 SuperGen 639 SEMI-SYNTHETIC VERSIONS 638 Samyang Genex 639 Xechem International 640 Aphios 638 Wex 639 NEXT GENERATION OF TUBULIN STABILIZING Biolyse Pharma 638 NOVEL DRUG DELIVERY SYSTEMS 639 DRUGS/SPINDLE POISONS 640 BioNumerik Pharmaceuticals 638 Guilford Pharmaceuticals 639 Epothilones 640 Bio-Technology General 638 Matrix Pharmaceuticals 639 Eleutherobin 641 Cytoclonal Pharmaceutics 638 NeoPharm 639 RPR-109881 641

LIST OF EXHIBITS

TITLE PAGE Number of In-patient Ovarian Estimated Stage Distribution of Oral Estimated Incidence of Pediatric Procedures in the USA 546 Cavity and Pharynx Cancer at Time of (Ages 0-19) Primary Brain Tumors by Surgeries and Outlays for Ovarian Diagnosis by Gender in the USA 1997 628 Histology Group and Gender in the USA 688 Cancer in Medicare Patients in 1995 547 Estimated Five Year Survival Rates of Estimated Incidence of Metastatic Brain Women Administered Chemotherapy Oral Cavity and Pharynx Cancer by Cancer by Primary Tumor in Selected for Ovarian Cancer in Selected World Gender in the USA, 1997 629 World Regions in 1997 689 Regions in 1995 550 Estimated Five Year Survival Rates for Molecular Markers for Brain Tumors and Chemotherapeutics Approved Worldwide Oral Cavity and Pharynx Cancer in Cancer of the Central Nervous System 690 for the Treatment of Ovarian Cancer 552 Major World Regions, 1997 630 Five-Year Survival Trends of Brain and Nervous System Cancer Cases Recently Reported Results from Various Correlation of Selected Growth Factor Clinical Trials in Ovarian Cancer 555 Expression and Survival in HNSCC 631 in the USA 694 Estimated Chemotherapy Treatment Estimated Incidence, Two- and Five-Year Active Ongoing Clinical Trials for the Regimens for Head and Neck Cancer Relative Survival for Malignant Brain Treatment of Ovarian Cancer 558 in Selected World Regions in 1997 632 Tumors by Histology Group 695 Screening/Diagnostic Tests on the Worldwide Candidate Populations Five-Year Survival Rates for Brain and Market and/or in Development for for Taxane-based Chemotherapy 636 Nervous System Cancer in the USA 6 Cervical Cancer 563 Response Rates Associated with in 1997 697 Diagnostic Triage with Pap and Taxane Therapy 640 Incidence and Five-Year Survival of Brain HPV Testing 566 Chemotherapy Regimens in Current and Nervous System Cancer in Selected Selected Agents in Development for Clinical Trials in HNSCC 649 World Regions by Stage at Diagnosis 699 the Treatment of Ovarian Cancer 572 Drugs in Development for the Surgical and Other Ablative Techniques Estimated Potential Market for Therapeutic Treatment of Head and Neck Cancer 652 in the Treatment of Brain Tumors 704 and Prophylactic Vaccines for Ovarian Estimated Radiation Therapy Cancer in Selected World Regions 585 Cost comparison of Inpatient Antibiotic Regimens in Neutropenic Patients 667 Cases of Primary CNS Cancer by Estimated Incidence and Mortality of Major World Regions 706 Estimated Worldwide Incidence of Oral Cavity, Pharynx and Larynx Cancer Radiotherapy Techniques in Clinical Use 708 in Major World Regions in 1997 607 Primary Brain and Nervous System Cancer in 1997 671 Estimated Chemotherapy Cases of Primary Estimated Worldwide Incidence of Head CNS Cancer by Major World Regions 710 and Neck Cancer (Oral Cavity and Estimated Worldwide Mortality of Pharynx) in 1997 608 Primary Brain and Nervous System Commercially Available Therapeutics Cancer in 1997 673 for the Treatment of CNS Cancer 711 Estimated Worldwide Mortality of Head Types of Benign and Primary Malignant Ongoing Clinical Trials with Commercially and Neck Cancer (Oral Cavity and Tumors of the CNS 676 Available Chemotherapeutics for Pharynx) in 1997 611 Estimated Annual Incidence of CNS Cancer 713 Estimated Incidence of Head and Neck Primary Brain Tumors by Site and Standard and Emerging Treatment Cancer (Oral and Pharynx) and Gender in the USA 680 Approaches For Primary and Metastatic Distribution by Site 613 Estimated Breakdown of Primary CNS Tumors by Histology Group Estimated Number and Percent of and Metastatic Adult Brain Tumors in the USA 719 New Cases and Deaths by Specific by Site in the USA 681 Outcome of Children with CNS Head and Neck Cancer Sites in North Tumors by Type 724 America (1997) 614 Incidence Rate of Brain and Nervous System Cancer by Race and Gender Worldwide Incidence and Mortality of Relative Five Year Survival Rate of Head Over Two Decades in the USA 685 Prostate Cancer in 1998 732 & Neck Cancer by Race in the USA 613 Estimated Incidence of Primary Age-specific Incidence of Prostate Molecular Markers Associated with Brain Tumors by Major Histology Cancer in Selected World Regions Head and Neck Cancer 616 Groups and by Gender in the USA 686 in 1998 735 Taxol Chronology 618 Estimated Incidence of Pediatric Estimated Age-specific Prevalence TNM Staging System for Head and Primary Brain Tumors by Gender of Latent Prostate Cancer in Selected Neck Cancer 627 and Age Group in the USA 687 World Regions in 1998 736

Incidence Trends of Prostate Cancer Drugs in Development for Treatment PSA Tests on the Market and/or in in the USA 737 of CNS Cancer 740 Development 767 Mortality Trends of Prostate Cancer Types of PSA Tests 763 Worldwide PSA Markets in 1997 771 in the USA 738 Prostate Cancer Markers 773 Incidence and Mortality Rates of Total PSA Tests Performed in all Men Prostate Cancer in the USA by Race and in Men Over Age 65 Between 1990 Gene Therapy Agents in Development and Ethnicity 739 and 1997 in the USA 765 by Introgen Therapeutics 776

INDEX OF COMPANIES & INSTITUTIONS

Aastrom Bioscience 572 Banyu 573 Cancer Research Campaign (CRC) Cortecs 574, 590, 628 Abbott Laboratories 579, 657, Bard Diagnostic Sciences 764 Centre for Cancer Therapeutics Coulter Pharmaceuticals 758 574, 590, 599, 600, 745, 786 662, 750, 757, 762, 764, 767 Bard Urological 764 Creighton University School Abic 552 Cancer Research Campaign of Medicine 547 Bar-Ilan Research and Development 572 Technology (CRTC) 599, 628, 736 AccuMed International 563 Cross Cancer Institute (CCI) BASF 576, 599 Cancer Therapeutics 573, 587, 588 Accuray 704 585, 714, 716 Bavarian Nordic Research Institute 740 Cancer Therapy and Advanced Biological Systems Cubist Pharmaceuticals 660 Bayer 563, 664, 757 Research Center 572 (ABS) 733, 740 Cyclacel 599, 600 Bayer Diagnostics 762, 763, 764, 767 Canji 573, 651, 652, 740, 777, 780 Agouron Pharmaceuticals Cytel 574 Baylor College of Medicine 595, 721 572, 622, 641, 650, 652 CarboMed 573 Cytoclonal Pharmaceutics 638 Beaufour Ipsen 648 Alamar Biosciences 563 Cascade Oncogenics 596, 597, 769 Cytogen 735, 745, 764, 769 Beckman Coulter 764 Alkermes 740, 752 Case Western Reserve University 558 Cytyc 563, 564 Beckman Research Institute Allergan Ligand Retinoid Castelfranco 713 Dabur 619 Therapeutics (ALRT) 572 of the City of Hope 558, 559, 560, 561 Catholic University 714, 718 Daiichi Pharmaceuticals 552, 574 Allos Therapeutics 738, 740 Behring Diagnostics 767 CDR Therapeutics 573, 586, 587 Dainippon Pharmaceutical 577 Almirall 552 Berlex 666, 757, 725 Cedar Sinai Medical Center 748 Damon Biotech 750 Alpha-Beta Technology 663 Bernardo Houssay Hospital 573, 652 Cel-Sci 652, 655 Dana-Farber Cancer Center 589 Alta Partners 587 Beth Israel Deaconess Cell Genesys 574, 579, 744 Medical Center 709 Dana-Farber Cancer Institute AltaRex 572, 584, 585 Cell Therapeutics 574, 656 560, 709, 746 Binary Therapeutics 709, 743 Alza 552, 553, 740, 752, 757 CellPro 576, 718 Dartmouth Medical School 576, 653, 742 BioChem Pharma 574 AMDL 767 Celltech Therapeutics 574 Darwin Discovery 785 BioChem Therapeutic 580, 743 American Home Products 554, 574, 617 Center for Molecular Medicine David Bull Labs 619 Biogen 725, 740 American Red Cross 652 and Immunology (CMMI) 575, 588 Debiopharm 571, 574 7 Biolyse Pharma 619, 635, 637, 638 Amgen 584, 731, 749, 759 Centers for Disease Control Degussa 653 and Prevention 659 Ampersand Ventures 563 Biomerica 767 Denvu 563 Centocor 773 Anchor Advanced Products 572 Biomira 572, 573, 584, 585, 586 DepoTech 574, 717, 718 Anika Therapeutics 572, 589 Biopharmaceutics 733, 740 Centre de Recherche pour les Pathologies Prostatiques (CEREPP) 765 DiagnoCure 774 Ansan 572 Boehringer Ingelheim 648, 653 Centre Leon Berard 713 Diagnostic Decisions 768 Anthra Pharmaceuticals 570, 572 Boehringer Mannheim Cephalon 574, 737, 740 Diagnostic Products AntiCancer 572, 581, 582 573, 652, 656, 768, 769 Corporation 762, 767 ChemGenics Pharmaceuticals 663 Anti-Cancer Center Paul Strauss 567 Bombay Hospital 716 Diagnostic Systems Laboratories 767 ChiRex 619, 638 Antigenics 572 Boston Scientific 754 Dianon 767, 768 Children’s Hospital at Harvard Boron Biologicals 706 Digene 563, 564 Antisoma 573, 587, 588 Medical School 741 BrainLAB 704, 705 Dillion, Read Ventures Capital 599 Aphios 638 Children’s Hospital of Philadelphia 740 Briana Bio-Tech 740 DPC Bierman 762, 767 Aphton 572 Chinoin 740 Appex Technologies 585 Brigham and Women’s Hospital Draxis Health 638 704, 707, 709, 716 Chiron 573, 574, Apothecon 665 576, 586, 656, 717, 741, 747, 750 Drug Royalty 638, 639 Bristol-Myers Squibb (BMS) Aquila Biopharmaceuticals 744 Chiron Diagnostics 764, 767 Duke Comprehensive 548, 549, 552, 553, Cancer Center 712, 715 Arch Partners 587 566, 567, 571, 573, 579, 599, 614, 616, Chiroscience 785 Duke University 576, 741, 744, 746 Ares Serono 552 617, 618, 619, 620, 635, 637, 639, 641, Cholestec 767 Dundee University 600 Arizona Cancer Center 578, 580 642, 650, 658, 663, 710, 711, 712, 723, CHU 716 733, 734, 735, 739, 740, 744, 746, 778 DuPont Merck Pharmaceuticals 599 Arizona State University 580 Chugai 553, 578, 635 British Biotech Arkansas Cancer Research Center 658 Eastern Cooperative Oncology 567, 573, 685, 740, 745, 746 Ciba Corning Diagnostics 767 Group (ECOG) 559, 636 Aronex Pharmaceuticals 573, 580, 662 British Columbia Cancer Ciba-Geigy 576 Edith Norse Rogers Memorial ArQule 662 Agency (BCCA) 585 CIS biointernational 767 Veterans Hospital 785 Arris Pharmaceutical 685 British Columbia Cleveland Clinic 715, 731 EG&G Wallac 762, 767 Ascalon 586 Children’s Hospital 715 Clinique de Pediatrie (Geneva, Elan 735, 745, 764 Asta Medica 573, 579, 653 Brookhaven National Switzerland) 716 Elekta Instruments 704 Astra Merck 753 Laboratory 706 Cobe BCT 572 Eli Lilly 552, 567, 574, 576, 577, Austin Research Institute 575 Buenos Aires University 565, 573, 652 Cold Spring Harbor Laboratories 751 581, 650, 659, 660, 662, 664 AutoCyte 563 Burnham Institute 770 Colorado State University 663 Elscint 683 AVAX Technologies 573, 585, Burr Egan Deleage 587 Columbia Presbyterian Emory University 736 Avigen 740, 749 C.R. Bard 764 Medical Center 713 EntreMed 741, 746 Axys Pharmaceutical 685 Calydon 573 Columbia University 562, 575, 751, 781 Environmental Protection Azienda Ospedaliera 716 Cambridge Antibody CompuCyte 563 Agency 637 Baker Norton Pharmaceuticals Technology (CAT) 745, 751 Corange International 652, 656 Enzon 647, 652 549, 571, 615 Cambridge NeuroScience 578 Corixa 574, 586 EORTC 559, 565

Ergo Science 589, 741 Hotel Dieu de Montreal Hospital 638 Lady Davis Institute Montana College of Mineral ESCAgenetics 639 Houghten Pharmaceuticals 662 for Medical Research 655 Science and Technology 638 Ethox 572 Howmedica Leibinger 705 Laserscope 753 Montana State University 638 F. H. Faulding 549, 552, 571, 619, 637 Human Genome Sciences 766, 774 Lederle Japan 648, 664 Morningstar Diagnostics 768 Florida State University 618 Humboldt University 779 Leica Microscopy and Systems 563 Mortimer B. Davis Jewish General Hospital 565, 655 Food and Drug Administration Hyal Pharmaceutical 652, 656 Leiden University 783 (FDA) 563, Hybritech 762, 763, 764, 767, 768, 769 Lescarden 576, 653 Mount Sinai Shool of Medicine 572 564 585, 590, 615, 616, 619, 620, Iatron Laboratories 768 Lexigen Pharmaceuticals 742, 750 Myco Pharmaceuticals 663 635, 636, 637, 638, 640, 762, 767, 768 Icos 600 Ligand Pharmaceuticals 576, MycoTox 663 Fordham University 572 IDEC Pharmaceuticals 575, 731, 741, 758 648, 650, 653, 740 Mylan Pharmaceuticals 638 Foshan Faulding 552, 619 Ilex Oncology 648, 741, 754 Lineberger Comprehensive Cancer Myriad Genetics 577, 751, 765 Fournier (Laboratoires) 580 Center UNC 560 Ilexus 575 Nagoya University 740 Fox Chase Cancer Center 583 Linz-Roberts 707 ImClone Systems Nanning Maple Leaf Pharmaceutical 639 Fred Hutchinson Cancer 575, 602, 643, 652, 654 The Liposome Company 665 NaPro BioTherapeutics Research Center 559, 686 Immune Response 741, 748 Loma Linda University 708 549, 552, 571, 615, 617, 619, 637 Fuji ImmunoPharmaceuticals 742, 750 Immunex 554, 572, 575, 601, Loma Linda University National Center for Human Fujisawa 665 602, 617, 619, 620, 666, 712, 756 School of Medicine 787 Genome Research (NCHGR) 766 Garden State Cancer Center 588 Immuno-Biological Laboratories 768 London Ontario Regional National Cancer Institute (NCI) 552, Cancer Center 638 GE Medical Systems 708 Immunomedics 575, 588 553, 558, 560, 562, 573, 575, 576, 577, Gene Logic 765 Louisiana State University 578, 580, 587, 597, 598, 599, 618, 635, Immutec 619 School of Medicine 786 641, 643, 652, 653, 670, 685, 707, 715, GeneMedicine 652, 656 Imperial Cancer Research Ludwig Institute for Cancer 732, 733, 734, 735, 736, 737, 738, 740, Genentech 574, 637, 758 Fund (ICRF) 575, 587, 588 Research 574 741, 742, 743, 744, 745, 746, 747, 775 Genetic Therapy 575, 741, 750, 782, 784 Imperial Cancer Research Ludwig-Maximilians-Universität 653 National Human Genome Technology (ICRT) 740 Research Institute (NHGRI) 766 Genetix Pharmaceuticals 575, 584 Lund University 762 Imperial College 663 National Institutes of Health (NIH) Genetronics 652, 657, 741, 752 Lundbeck 552 GenQuest 781 Indena 617, 618 552, 562, 575, 577, 578, 734, M. D. Anderson Cancer Center 735, 738, 741, 743, 756, 773, 784, 785 Genset 765 Indiana University School 558, 560, 575, 576, 578, 580, of Medicine 576 National Testing Laboratories 563 Gensia Sicor 638 584, 590, 640, 651, 652, 653, 661, 662, Indigo Medical 646 NCI Division of Cancer Treatment, Genzyme 575, 780 746, 705, 713, 714, 715, 716, 751, 776 Inex 576 Diagnosis and Centers 647 Genzyme Molecular Oncology 780 Magainin Pharmaceuticals 742 Ingenex 576, 584 Nehoc 585 Genzyme Transgenics 580, 586 Magenta Pharmaceuticals 584 InNova 619 Mallinckrodt Medical BV 683 NeoPath 563 Georgetown University NeoPharm 577, 639, 707, 738, 743 574, 580, 639, 746 Instent 754 Massachusetts General Hospital (MGH) 588, 689, 708 NeoRx 577, 588 Gesellschaft für Biotechnologische Institut für Klinische Hamatologie 576 8 Forschung 641 Institute for Cancer Research Massachusetts Institute of The Netherlands Cancer Institute 631 Technology (MIT) 563, 593, 639, 706 Gilead Sciences 600 574, 590, 652, 655 Neurobiological Technologies 725, 743 Matritech 563, 768 Glasgow University 600 Institute of Virology 740 Neuromedical Systems 564 Matrix Pharmaceuticals 576, 639, 653 Glaxo Wellcome Instituto de Ricerche di New York University Medical Center 579 552, 553, 554, 575, 581, 599, 600, Biologia Molecolare 602 Max-Planck Society 579 NeXstar Pharmaceuticals 642, 650, 660, 662, 664, 718, 758, 786 Intermountain Health Care 558 Maxim Pharmaceuticals 755 577, 578, 639, 665 Goodwin Biotechnologyx (GBI) 580, 586 International Isotopes (I3) 705 Mayo Clinical Cancer Center Nikon 563 Grupo Ferrer Internacional 662 Introgen Therapeutics 576, 642, 559, 714, 716, 724 Nippon Kayaku 573 651, 652, 653, 654, 769, 775, 776, 777 GSF-Forschungszentrum für McGill University 565, 638, 768 Nomos 708 IntroGene 741 Umwelt und Gesundheit 740 Mead Johnson Oncology 552 Norris Cotton Cancer Center 557, 715 Ion Beam Applications 704 Guilford Pharmaceuticals Medac 552, 572, 584 Norwegian Radium Hospital 713 639, 710, 711, 741 Ireland Cancer Center 558 Medarex 576, 653, 655, 742 Nova Therapeutic Systems 704 Hafslund Nycomed 620 Isis Pharmaceuticals 576, 781 Medeva 570, 571, 572 Novartis 575, Hamilton Regional Cancer Centre 655 Ivax 549, 571, 615, 616, 635, 637 Medical Research Council (UK) 558 576, 577, 583, 623, 641, 741, 743, 784 Harvard Medical School Janssen Pharmaceutica 577, 588, 741 MediCorp 768 Novopharm Biotech 743 635, 704, 707, 708, 709 Jefferson Medical College 697 Meditech 577 Nycomed Pharma 549, 554, 707, 742 Harvard University 589, 599 Jenner Technologies 576 Medtronic 754 Olympus America 563 Hauser 616, 617, 618, 620, 637 Jewish General Hospital in Montreal 638 Meiji Seika Kaisha 660 OncoAntigenics 572 HealthCare Investment 599 John Wayne Cancer Institute 714, 737 Meiji Seika Pharma International 579 OncoRx 648 Helsinki University Central Hospital 762 Johns Hopkins Oncology Center Memorial Sloan-Kettering Cancer OncoTech 577, 743 Henry Ford Hospital 684 560, 712, 714, 716, 735 Center/Sloan-Kettering Institute for Onyx Pharmaceuticals Johns Hopkins University HepaVec 779 Cancer Research 558, 560, 574, 577, 577, 599, 600, 653, 654, 695, 778 579, 639, 672, 696, 742, 766, 768 597, 735, 714, 744, 746, 769, 784 Herbert Irving Comprehensive OPG/Pharmachemie 549, 554, 620 Cancer Center 714 Johnson & Johnson 588, 646, 656 Merck 658, 662, 663 Oregon Health Sciences University 597 HFR Unit, JRC-IAM, European Johnson & Johnson MerckFrosst Canada 572, 584 Orion Pharma (Orion Farmos) 711, 741 Commission 706 Development Corporation 584 Merck KGaA 653, 655, 742, 768 Ortho Biotech 656, 756 Hoechst Celanese Kagoshima University 734, 745 Merck Research Laboratories 694 Fine Chemicals 647, 653 Osaka University Kaiser Permanente 564, 565 Merlin Ventures 599, 600 Hoechst Marion Roussel 587, Medical School 734, 745 Khepri Pharmaceuticals 685 metaGen 765 598, 599, 658, 659, 660, 757 Ottawa Regional Cancer Centre 714 King Faisal Specialist Hospital Metastatin Pharmaceuticals 774 Hoffmann-La Roche 563, and Research Center 720 OUR Scientific International 704 MGI Pharma 577, 656 572, 599, 660, 622, 650, 652, 656, 756 Kissei 656 OXiGENE 578, 709, 743 Milkhaus Laboratory 577 Hokkaido University School Knoll AG 576, 599 Pacific Biotechnologies 617 of Medicine 783 Millennium Pharmaceuticals 663, 765 Kumamoto University Pacific Generation Horus Therapeutics 767 School of Medicine 752 Miravant Medical Technologies 742 Technologies 617 Hospital Notre Dame 655 Kyowa Hakko Kogyo Mitotix 599 Pacific Northwest Research Hospital Saint-Louis 765 553, 574, 598, 736, 742 Montana Biotech 663 Foundation 769

Pacific Pharmaceuticals Salpetriere Hospital 716 Terrapin Technologies 580, 583 University of Texas 558, 560, 575, (formerly Xytronyx) 709, 734, 743 Samyang 639 Teva 552 576, 579, 580, 583, 653, 661, 735, 743 Parke-Davis 578, 734, 735, 743 Samyang Genex 639 Texas Children’s Hospital 721 University of Texas Health Science Center, San Antonio 718 Paterson Institute of Sandoz 583 Theragenics 646 Cancer Research 628 University of Texas Sanofi 571, 574, Therion Biologics 580 Pennsylvania State College Southwestern Medical Center 658, 687 623, 642, 647, 648, 653, 709, 741, 744 Thomas Jefferson University 573, 585 of Medicine 738, 743 University of Utah 577 Sanofi Diagnostics Pasteur 764 Titan Pharmaceuticals 580, 586 Pennsylvania State University 734, 743 Schering AG 571, 765 University of Washington Pfizer 660, 663, 665, 666, 754 Toronto Hospital 714 574, 586, 590, 698 Schering-Plough Toshiba America Medical Systems 681 Pharmachemie 549, 554, 756 552, 573, 579, 599, 643, 651, 652, 655, University of Western Ontario 713 Pharmacia & Upjohn 552, 658, 660, 662, 736, 740, 744, 751, 777 Tosoh 768 University of Wisconsin 593 553, 574, 575, 578, 599, 621, 656, 660, Schering-Plough Research Towers Phytochemicals 638 University of Vaudrois 742 712, 717, 718, 739, 742, 755, 757, 779 Institute 777, 778 TPL Phytogen 638 University of Virginia 643 Pharmacopeia 662 Schneider 754 Transgene 580 UroCor 765, 768, 774 Pharmacyclics 647, 653, 707, 743 Scotia Holdings 578, 648, 653, 744 Transmolecular 745, 747 UroGenesis 769 Pharma Mar 578 Scripps Institution of Oceanography 641 Trega Biosciences 662 U.S. Bioscience Pharos Pharmaceutical 639 Scripps Research Institute Triangle Pharmaceuticals 552, 553, 656, 724, 733, 745 618, 641, 742, 750 731, 732, 733, 745 Phoenix Pharmaceuticals 743 Vanderbilt University 590 SeaMED 572 Trilex Pharmaceuticals 580, 586 Physician’s Reliance Network 778 Varian Associates 704 SepraChem 638 Trylon 564 Phytogen International 638, 639 Varian Oncology Systems 708 Phytogen Life Sciences 638, 639 Sequus Pharmaceuticals Tufts University 572 554, 570, 571, 579, 636, 653, 665 Ventana Genetics 600 Phyton 618 Tulane University 573, 786 Seragen 579, 744 Vertex Pharmaceuticals 580 PHYTOpharmaceuticals 639 Tumor Immunology and Gene Serono Laboratories 744 Vical 574, 586, 653 Picker International 683 Therapy Center 783 Shenzhen Boda Natural VIMRX Pharmaceutical 734, 745 Pierre Fabre 553 Universal Medical Systems 704 Product Company 638 Universitet i Umeå 766 Vincent T. Lombardi Cancer Center Princess Margaret Hospital Shimadzu 683 at Georgetown Medical Center for Children 713, 714, 715 University Hospital of Heraklion 667 Shionogi 572, 582 574, 580, 716, 746, 787 Princeton University 602 University of Alabama Vion Pharmaceuticals 648, 653 Sidney Kimmel Cancer Center 576, 575, 580, 588, 590, 643, 745, 747, 780 Prodesfarma 572 652, 653, 697, 741, 748, 770, 776, 781 Virginia Commonwealth University Progenics Pharmaceuticals 744 University of Alabama Medical College of Virginia 787 Siemens Medical Systems 682 Comprehensive Cancer Center 716 ProScript 599 Vital Pharmaceutical Development 580 Siemens Medical Systems, University of Alberta 572, 740, 783 Prototek 685 Oncology Care Systems 708 Walden Laboratories 585 University of Arizona 578, 580 Purdue University 576 Simmons Cancer Center 715 Walter Reed Army Institute University of Bologna 714 QLT PhotoTherapeutics Sittona Company BV 652 of Research (WRAIR) 576 University of California 648, 653, 709, 753 Warner-Lambert 599, 654, 660 9 SmithKline Beecham 577, 733, 744, 749 Quantimetrix 768 549, 553, 581, 664, 712, 757 Washington State University University of California, Research Foundation 638 R.W. Johnson Pharmaceutical Sofamor Danek Group 705 Irvine (UCI) 571, 577 Research Institute 656 Washington University 592 Sofinnova 587 University of California, Rabin Medical Center Somatix Therapy 579, 744 Los Angeles (UCLA) 546, 769 Wayne State University 655 at Tel Aviv University 655 Southern Research University of California, West Virginia University 716 Radionics 704 Institute 552, 709, 744 San Diego (UCSD) Wex 639 Repligen 578 Southwest Oncology Group 601, 652, 732, 744, 745, 750 Whitehead Institute 579 Research Corporation (SWOG) 559, 561 University of California, World Health Organization (WHO) 562 Technologies (RCT) 578, 580 Sparta Pharmaceuticals 639, 653 San Francisco (UCSF) Research Triangle Pharmaceuticals 639 694, 722, 740, 743, 749, 750, 777, 784 Wyeth-Ayerst Speywood Pharmaceutical 648 574, 575, 580, 602, 617, 620, 663 RGene Therapeutics 580 University of Chicago 560, 576, 584 The Sprout Group 563, 587 Xechem International 640 Rhône-Poulenc Rorer SRI 653 University of Cincinnati 651 549, 552, 553, 575, Xenova 745 SRI International 707 University of Colorado 578, 581, 614, 620, 621, 635, 641, 650, Cancer Center 714 Yakult Honsha 552 652, 659, 711, 712, 741, 744, 769, 775 State University of New York 782 University of Colorado Health Yale Comprehensive Cancer Center 558 Staten Island University Ribi ImmunoChem Research 573 Sciences Center 619 Hospital North 716 Yale University 648, 653, 747 RiboGene 662 University of Dundee 599, 600 Stehlin Foundation for Yang 768 Roberts Pharmaceuticals 707, 742 Cancer Research 575 University of Iowa 716 Yew Tree Pharmaceuticals Roche 708 Strong Memorial Hospital 712 University of Kentucky 549, 554, 619, 620, 637 Roche Diagnostic Systems 768 Sugen 579, 587, 599, 653, 738, 744 Research Foundation 580, 586 Zelenka Nursery 617 Roche Holdings 769 Sun Hill Glucose 639 University of Lund 709, 762 Zeneca 573, 622, 653, 654, 665 Roche Image Analysis Systems SUNY at Buffalo School University of Michigan 572, 653 (RIAS) 563 of Medicine 713 University of Montreal 638 Roger Bellon 552 SuperGen 639, 640 University of Pennsylvania Roswell Park Cancer Institute 602 Supratek Pharma 744, 752 573, 587, 745, 749, 784 NOTE: The Rowland Institute 741 Surgical Navigation Technologies 705 University of Pittsburgh 580, 653, 656, 768, 769 OUR AREA CODE HAS Royal Marsden Hospital 574, 590 Synthelabo 765 University of Rochester 724 BEEN CHANGED Royal Prince Alfred Hospital 716 Taiho Pharmaceutical 580, 583, 734, 745 University of Rome La Sapienza 661 RPR GenCell Takara Shuzo 659 576, 584, 642, 651, 652, 653, 775 University of Southern TELEPHONE: Takeda 579, 744, 746, 764 Rush Presbyterian St. California (USC) 557, 635, 694, 748 Tanabe Seiyaku 573, 740, 746 (949) 830-0448 Luke’s Medical Center 657 University of Southern California TAP Pharmaceuticals 579, 744, 746, 764 Saint Joseph’s Hospital and at San Diego 636 FAX: Medical Center 588 Targeted Genetics 580 University of South Florida 657 (949) 830-0887 Saint Jude Children’s Targon 735, 745, 764 University of Tennessee Research Research Hospital 715 Techniclone 745, 751 Corporation (UTRC) 580

REPORTS

CANCER PAIN: WORLDWIDE PRODUCT Section VI provides a detailed review of R&D involving significant improvements of existing drugs such as opioids and non-opioids DEVELOPMENT AND MARKET OPPORTUNITIES as well as novel agents based on newly-discovered mechanisms, REPORT #430 SEPTEMBER 1998 250 PAGES $3,450 including ion channel blockers, afferent neurons, ligand/receptor interactions (neurotransmitters, NMDA antagonists, neuropeptides, One of the most debilitating complications of cancer is moderate cholecystokinin antagonists, etc.), anti-hypersensitivity agents, to severe chronic pain. Ignored in the past, new guidelines call for etc.This Section also incorporates a comprehensive database aggressive treatment of such pain and are encouraging physicians of analgesics in development worldwide, listing the agent’s devel- to co-operate with their patients to achieve satisfactory control. oper/ affiliate, mechanism/technology and clinical status. Currently, the most effective agents in the treatment of cancer pain Section VII estimates current worldwide markets for pain are opioids but considerable R&D effort is underway to discover and management products and identifies major opportunities commercialize alternative pharmacologic treatments promising to for cancer-pain medications. improve the quality-of-life of chronic pain sufferers irrespective of the origin of pain.This report provides a comprehensive review of all Section IX profiles over 40 developers of pain-related aspects of cancer pain as outlined below: products. Section I describes the basic mechanisms involved in pain Molecular Biology of Pain (pain receptors and signal transmission pathways) CANCER VACCINES: TECHNOLOGY, PRODUCTS, Anatomy of Pain Perception (peripheral receptors, spinal MARKETS AND BUSINESS OPPORTUNITIES cord, brain regions and pathways) Types of Cancer-Related Pain (bone, breakthrough, REPORT #401 250 PAGES OCTOBER 1997 $1,950 central, neuropathic, nociceptive, phantom and treatment- related pain) Increased understanding of the immune system coupled with Physiology and Pathogenesis of Pain (cancer types and genetic engineering and other cutting-edge technologies, is encour- special populations) aging the development of a new generation of vaccines using 10 diverse approaches. A new round of prototype tumor vaccines is Section II provides a worldwide epidemiology of incidence, expected to advance in clinical trials in the next two to three years. prevalence and morbidity associated with cancer pain by origin Some vaccines represent a broad-based approach, attempting to and world region (North America, Europe, Japan and ROW) and assesses its economic and quality-of-life impact. trigger the whole immune system, while others are directed at specific targets. If successful, cancer vaccines will first be used thera- Section III describes diagnostic and management approaches peutically, to boost the immune response to cancer in patients by origin of pain already afflicted. A vaccine that would actually prevent cancer in Tumor-related Chronic Pain Syndromes high-risk individuals will be the next step, although this is probably Treatment-related Chronic Pain Syndromes years away. NEW MEDICINE has just released a cancer vaccine report providing an in-depth analysis of the cancer vaccine sector Section IV delineates current treatment approaches (see page 5). This report provides a comprehensive analysis of the Pharmacologic Interventions (NSAIDs, morphine/opioids, cancer vaccine sector in terms of: basic science (tumorigenesis, methadone, corticosteroids, alpha adrenergic agonists, anticon- oncogenes, tumor-suppressor genes, mitogenic growth factors and vulsants, antidepressants, neuroleptics, biphosphonates/calci- tonin, antineoplastics, muscle relaxants, antihistamines, psy- growth inhibitory factors, viral causes, apoptosis, immune response, chostimulants, etc.) tumor antigens, immune surveillance); technology (antiviral vac- Radiation Therapy (treatment of bone metastases by cines against cancer, nonspecific and specific active immunothera- localized, wide-field, stereotactic and fractionated radiotherapy py, whole tumor cell vaccines, gene transfer, protein antigens, adop- and radiopharmaceuticals) tive immunotherapy, activated killer cells, tumor-infiltrating lympho- Surgery and other Approaches (neurosurgery, nerve cytes, passive immunotherapy, adjuvants); indications and epi- blocks, acupuncture, psychosocial interventions) demiology (worldwide incidence by disease severity and survival and mortality statistics for major cancers); products under Section V describes drug delivery methodologies in use or development (a comprehensive database of over 160 cancer in development to enhance administration of pain medications, vaccines in development worldwide, including data on develop- including oral controlled/sustained release, rectal, transdermal, nasal/inhaled, injectable, intrathecal/intraspinal (temporary/ er/affiliate, technology and clinical status); market opportuni- permanent catheters, subcutaneous injection ports/reservoirs, ties worldwide (by indication based on candidate populations implantable pumps, intraventricular delivery, patient-controlled and suggested treatment costs); and developer profiles (over analgesia, encapsulated cells, etc.) and subarchnoid delivery. 60 companies).

NEW MEDICINE, the publisher of FUTURE ONCOLOGY, mucositis, neutropenia, pain, thrombocytopenia, xerostomia, the premier analytical newsletter in the oncology field etc.). Each record contains information on every aspect of has released a comprehensive resource, Oncology the agent in development. For instance, do you need to know: KnowledgeBASE, to keep its clients informed of developments in the cancer field. How many drugs are in development based on the NM/OK is a resource developed for the executive/profes- mechanism of angiogenesis? (about 40) sional working in the oncology field. This is not another piece of the puzzle but a comprehensive all-in-one listing of Who is the developer? everything you wanted to know about this field, updated Is there a collaboration and with whom? daily. NM/OK was designed to reside in one’s computer at What is the status of the drug? one’s desk and allow immediate and convenient access to How is it administered? etc. information in this field. For instance, when a competitor releases clinical results of a novel agent in development, the How many drugs are in development for prostate NM/OK subscriber can instantaneously compare these cancer? (140) results with those of other agents in development for the How many are in phase III? (21) same or a related indication. When a new affiliation/collabora- How many of these are oral agents? (7) tion is announced between two companies or a licensing agreement with an academic institution, NM/OK lets one What are the results of clinical trials? etc. review all other affiliations/collaborations of the key players. How many drugs are there in the Pharmacia & Upjohn The oncology field is advancing at a breakneck pace with pipeline? (8) and those of its affiliates? (5) new developments in basic science, progress in preclinical What is the status of these drugs? 11 research, and results of clinical evaluations being reported on a daily basis and new drugs being approved for indica- Which companies have forged alliances with Bristol- tions for which no new drugs had been introduced for Myers Squibb? [Chiroscience Group, EntreMed, decades. History will view the 1990s as pivotal years in the Pharma Mar, Progenics Pharmaceuticals, Somatix war against cancer but there is still a long way to go before a Therapy (Cell Genesys), etc.]; for what cure is found. products/enabling technologies? NM/OK was designed to be used by executives who need to follow closely any developments in this area, in terms of: How many drugs in development are orally bioavailable? (73) • product development status • competitive pipelines How many of these are in clinical trials? (51) • affiliations How many drugs are in preclinical trials? (257); • novel drug development opportunities in research? (121); in phase I? (260) • clinical development status How many drugs have been discontinued in the last • current worldwide epidemiology several years? (18); how many of these were in phase • current worldwide sales of commercially available agents III clinical trials? (6) • market opportunities of agents in development Why were they discontinued? NM/OK consists of a number of modules (New Drugs, Marketed Drugs, Companies, Diagnostics, Devices, How many affiliations have been concluded by M. D. Epidemiology, Markets, Indications, Technologies, Mechanisms, Anderson Cancer Center? (14) Drug Delivery, Markers, etc.) covering every important aspect of the cancer field. The currently available module, New Drugs, incorporate over 950 records of agents in development for cancer and A UNIQUE ELECTRONIC RESOURCE complications associated with the disease and its treatment IN THE CANCER FIELD. (anemia, cachexia, edema, emesis, hypercalcemia, infection,

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