DOCSLIB.ORG

High-Dose Busulphan/Melphalan with Autologous Stem Cell Rescue in Ewing’S Sarcoma

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
High-Dose Busulphan/Melphalan with Autologous Stem Cell Rescue in Ewing’S Sarcoma Bone Marrow Transplantation, (1997) 20, 843–846 1997 Stockton Press All rights reserved 0268–3369/97 $12.00 High-dose busulphan/melphalan with autologous stem cell rescue in Ewing’s sarcoma A Atra1, JS Whelan,2 V Calvagna1, AG Shankar1, S Ashley1, V Shepherd1, RL Souhami2 and CR Pinkerton1 1Department of Paediatric Oncology, The Royal Marsden NHS Trust, Sutton; and 2The Meyerstein Institute of Oncology, The Middlesex Hospital, London, UK Summary: Patients and methods Eighteen patients with poor risk Ewing’s sarcoma Eighteen patients were entered into the study. There were (including 11 patients with metastatic disease at nine females. The median age at diagnosis was 14.2 years presentation) received consolidation therapy of busul- (range 2.75–30 years). Primary tumours were of the central phan and melphalan with autologous stem cell rescue. skeleton in 10 cases and long bones in eight cases. Eleven There were nine females. The median age at diagnosis cases were metastatic at initial presentation, 10 with pul- was 14.2 years (range 2.75–30 years). There was one monary disease and one with bone marrow involvement. early death due to cytomegalovirus pneumonitis. One The primary tumour of the metastatic cases was central patient developed a single generalised convulsion during skeleton in six, and long bones in five cases. Six of the busulphan therapy. Severe renal toxicity was not seven non-metastatic patients had bulky primary tumours encountered. One patient developed veno-occlusive dis- (>100 ml) and the seventh patient was in second complete ease of the liver (VOD) which eventually resolved. With remission at the time of high-dose therapy. In total 12 a median follow up of 2 years, 13 patients survive patients were in first complete remission (CR1), four in including six with initial metastatic disease. We con- CR2, one in partial remission (PR) and one with progress- clude that high-dose busulphan/melphalan is well-toler- ive disease (PD) at the time of HDT. The characteristics of ated and should be evaluated for efficacy in a larger these patients including their initial chemotherapy are series of patients with high risk Ewing’s sarcoma. shown in Table 1. Keywords: busulphan/melphalan; high-risk Ewing’s Pretreatment investigations besides clinical evaluation sarcoma; autologous stem cell rescue included radiological assessment (CT scan and/or MRI) of all measurable disease, haematological and biochemical parameters, bone marrow aspirate/trephine and assessment of renal function including glomerular filtration rate. Daily The introduction of combined modality treatment has led measurement of haematological and biochemical para- to a rapid improvement in the prognosis for many patients meters were done from day 1 post-stem cell re-infusion 1–3 with Ewing’s sarcoma. However, the results from indi- until recovery. Informed verbal consent regarding the use vidual centres and cooperative groups have consistently of the drug combination and stem cell harvest procedure identified the inferior prognosis of patients with large vol- was obtained from the parents, or patients, of all cases ume primary tumours and/or metastatic disease.4,5 entered into the study. High-dose chemotherapy with autologous stem cell res- cue (bone marrow and more recently peripheral blood stem cell (PBSC)) is under evaluation in the management of Treatment 6–9 many cancers, particularly haematological malignancies. All patients were treated with busulphan 16 mg/kg (14 Ewing’s sarcoma may be a suitable disease for this strategy patients) or 600 mg/m2 (four patients), orally over 4 days because of its sensitivity to alkylating agents. Several small in 6 hourly divided doses, after 12 h prehydration, from studies have suggested that some patients with poor risk day −5to−2 prior to stem cell re-infusion. This was fol- 10–13 Ewing’s sarcoma may benefit from high-dose therapy. lowed by the intravenous infusion of melphalan at a dose The combination of busulphan/melphalan has been used in of 160 mg/m2 (11 patients) or 140 mg/m2 (six patients) on patients with acute or chronic myeloid leukaemia and other day −1. Cryopreserved autologous stem cells, bone marrow 14–16 solid tumours. This report describes the combined (BM) (seven patients), peripheral blood stem cells (PBSC) experience of two centres using a single regimen, busul- (seven patients) or both (four patients), were infused on the phan and melphalan followed by autologous stem cell following day (DO), at least 48 h after completion of the rescue in patients with Ewing’s sarcoma. busulphan course (Table 2). PBSC were harvested without the use of growth factors Correspondence: Dr A Atra, Department of Paediatric Oncology, The in 11 patients and cyclophosphamide and G-CSF priming Royal Marsden NHS Trust, Downs Road, Sutton, Surrey, SM2 5PT in seven patients. PBSC harvests were timed after chemo- Received 22 March 1997; accepted 26 June 1997 therapy for maximum yield (in non-primed patients) and Busulphan/melphalan in Ewing’s sarcoma A Atra et al 844 Table 1 Details of patients and prior treatment Table 2 Type and dose of stem cell rescue Sex Age Site Previous treatment Stem cell MNC 108/kg CFU-GM 104/kg Time of HDT (year) BM 3.09 8.4 CR1 F 15 L iliac bone IVAD × 4; surgery; DXT; BM 2.24 NK CR1 VP/Ifos × 2 BM 2.73 10.6 CR1 + F 16 R iliac bone IVAD × 4; surgery; VP/Ifos BM PBSC 3.06 15.43 CR1 × 2 BM 1.26 17.02 CR1 BM 4.66 36.9 CR1 × M 12 R tibia IVAD 4; surgery; VP/Ifos BM + PBSC 2.65 17.4 CR1 × × 3, IVA 2 BM + PBSC 6.05 7.54 CR1 F 8 R femur IVAD × 4; surgery; VP/Ifos BM 1.6 12.9 CR1 × 3BM+PBSC 5.49 3.08 CR1 M 12.15 L iliac bone, IVAD × 4; surgery; VP/Ifos BM 1.64 10.63 CR1 Scapula and bone × 2; DXT PBSC 4 40.5 CR1 marrow PBSC 3.8 26.9 CR2 PBSC 1.4 28.1 CR2 × × M 16.5 Second and fifth IVAD 4; VP/Ifos 2 PBSC 6.0 NK PR1 metatarsals and No surgery or DXT PBSC 5.4 59.1 PD lungs PBSC 5.6 66.7 CR2 M 9.75 R pubic bone IVAD × 4; surgery; VP/Ifos PBSC NK NK CR2 R lung × 3 M 13.6 Pubic bones IVAD × 4, IVA × 2; DXT; NK = not known; PD = progressive disease. Lungs VP/Ifos × 2, VAC × 2 F 2.75 Cervical (C3) IVAD × 6; VP/Ifos × 2 vertebra No surgery or DXT patients who remain in complete remission, including six F 17.3 Iliac bones, skull, IVAD × 4; VP/Ifos × 3; with metastatic disease (five lungs and one bone marrow) sacrum and lungs CYVAD × 3 at diagnosis (Figure 1). No surgery or DXT Five patients relapsed after high-dose therapy (two pul- M 13 L iliac bone IVAD × 4; DXT, IVA × 2; × monary, two in other bones and one in bone marrow). All VP/Ifos 2 have died except one patient who relapsed in the lung × M 30 R thigh & lungs EVAIA 8; surgery (single lesion) 7 months after busulphan/melphalan. He sur- + + + F 25 R scapula and Epi VCR Cyclo DTIC vived following lobectomy and unilateral whole lung radio- lungs × 3; DXT; EVAIA × 8 therapy and is alive in complete remission 18 months post- F 18 R femur, R lung VAIA × 4; surgery; DXT; pleura EVAIA × 3 high-dose therapy. Neutrophil .0.5 × 109/l occurred at a median of 12 days M 12 R humerus and EVAIA × 8; CbEC × 2; lungs DXT (range, 10–24 days) with a slower platelet recovery .50 × 109/l ranging from 24–52 days post-stem cell rescue. M 14 R pelvis and lung EVAIA × 8; CbEC × 2; DXT One patient experienced a single grand mal convulsion last- F 14 L femur and IVAD × 4; CbEC × 4; DXT ing 5 min during busulphan despite prophylactic phenytoin lungs measured at therapeutic levels, with no sequelae. There was F 9 R femur IVAD × 4; surgery; CbE × one toxic death, at day 51 due to pulmonary haemorrhage 4; DXT secondary to cytomegalovirus infection. Mucositis (WHO grade IV) and diarrhoea (WHO grade II–IV) requiring anal- IVAD = ifosfamide, vincristine, adriamycin; VP/Ifos = gesia were documented, and total parenteral nutrition was etoposide/ifosfamide; IVA = ifosfamide, vincristine, actinomycin; VAC = required in all patients. All patients required at least one vincristine, actinomycin, cyclophosphamide; CYVAD = cyclophospham- ide, vincristine, adriamycin; EVAIA = etoposide, vincristine, actinomycin/adriamycin, ifosfamide; DTIC = dacarbazine; CbEC = car- boplatin and etoposide, cyclophosphamide; DXT = local irradiation. 100 usually performed on two separate occasions to maximise 80 mononuclear cell counts. Phenytoin at a dose 8 mg/kg/day orally in two divided 60 doses was commenced 2 weeks prior to busulphan as prophylaxis against neurotoxicity and continued until 48 h 40 after the last dose of busulphan. No prophylactic antibiotics were used. Only one patient received G-CSF (5 mg/kg/day) + 20 post-stem cell rescue from day 10. % Probability of survival 0 Results 012345678 With a median follow-up of 2 years, (range 2 months–7 Years since bone marrow transplant years) after high-dose therapy there are 13 surviving Figure 1 Survival after bone marrow transplant. Busulphan/melphalan in Ewing’s sarcoma A Atra et al 845 course of systemic antibiotics for episodes of febrile neutro- etoposide with encouraging results as compared to histori- penia with addition of systemic antifungal agents in the cal control groups.18,19 majority of patients. One patient developed clinical and bio- Other nonrandomised studies using high-dose alkylating chemical features of VOD which resolved. Another patient agents ± TBI failed to demonstrate any benefit in poor risk developed haemorrhagic cystitis which continues to recur patients.20 The combination of busulphan/melphalan has but which required no intervention.
Load more

Recommended publications
  • Hodgkin Lymphoma Treatment Regimens
    HODGKIN LYMPHOMA TREATMENT REGIMENS (Part 1 of 5) Clinical Trials: The National Comprehensive Cancer Network recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. Classical Hodgkin Lymphoma1 Note: All recommendations are Category 2A unless otherwise indicated. Primary Treatment Stage IA, IIA Favorable (No Bulky Disease, <3 Sites of Disease, ESR <50, and No E-lesions) REGIMEN DOSING Doxorubicin + Bleomycin + Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + Vinblastine + Dacarbazine vinblastine 6mg/m2 IV over 5–10 minutes + dacarbazine 375mg/m2 IV over (ABVD) (Category 1)2-5 60 minutes.
    [Show full text]
  • Desmoid Tumors: Understanding Treatment Options in 2019
    Desmoid Tumors: Understanding Treatment Options in 2019 Breelyn A. Wilky, MD Associate Professor Sarcoma Program, Division of Oncology A real desmoid story… 35 year old female physician who noted abdominal cramping and pain in her mid abdomen and a palpable mass in August 2018 She performed an ultrasound on herself in the ER which showed a 4.5 x 4.5 cm mass in her mid abdomen CT scan showed a mesenteric mass that was wrapped around and blocking the inferior mesenteric vein with multiple satellite nodules/lymph nodes. Biopsy confirmed the diagnosis of desmoid tumor A real desmoid story… Mother had a neuroendocrine cancer in the appendix, father had Hodgkins lymphoma The patient had a negative colonoscopy for any polyps She had no other medical problems but has three children, with the last baby born 4 months prior to her symptoms. This most recent baby was conceived with in vitro fertilization. Tumor board discussion… Ongoing pain likely related to venous outflow obstruction (confirmed on colonoscopy as well) Treatment options in 2019… Watch and Wait • Doxorubicin/ Dacarbazine Chemotherapy Attempt • MTX/vinblastine (IV) Surgery • Doxil • Sorafenib • Imatinib Targeted • Pazopanib treatments Radiation • Nirogacestat (chemo pills) • Tegavivint (IV) • Tamoxifen +/- sulindac Estrogen- Ablation • Aromatase blocking IRE/Nanoknife inhibitors Treatments HIFU • Celebrex Choosing a treatment approach . Anxiety over “doing nothing” . How long is acceptable to wait for Symptoms a response? Location . Can shrinkage or necrosis create a Risk to surrounding structures more definitive option? (surgery, and organs electroporation?) Growth pattern over time . What is the expected function or appearance after my desmoid Obvious estrogen exposure surgery? (pregnancy) .
    [Show full text]
  • Systemic Therapy for Advanced Soft Tissue Sarcoma
    Systemic Therapy for Advanced Soft Tissue Sarcoma a, b Jennifer Y. Sheng, MD *, Sujana Movva, MD KEYWORDS Advanced soft tissue sarcoma Chemotherapy Novel therapies KEY POINTS Survival for advanced soft tissue sarcomas has improved significantly over the last 20 years because of advancements in histologic classification, improved treatment ap- proaches, and novel agents. An important factor guiding choice of therapy is soft tissue sarcoma subtype, as drugs such as eribulin and trabectedin may have particular activity in leiomyosarcoma and liposarcoma. Focus on angiogenesis inhibition has led to the approval of pazopanib for soft tissue sar- coma, and the pathway continues to be investigated in this disease. Toxicity is an important area of investigation in soft tissue sarcoma, and new agents, such as aldoxorubicin, may be alternatives with better safety profiles. Future studies on treatment of advanced soft tissue sarcoma will continue to focus on identification of novel drug targets, personalization of therapy, and combination immunotherapies. BACKGROUND Sarcomas are rare tumors that arise from or are differentiated from tissues of meso- dermal origin. They comprise less than 1% of all adult malignancies.1 In 2015 there were approximately 14, 900 new cases diagnosed, with 6360 deaths in the United States. Sarcomas are grouped into 2 general categories: soft tissues sarcomas and primary bone sarcomas, which have different staging and treatment approaches. This article includes a discussion of chemotherapy in advanced or refractory soft tis- sue sarcoma. Patients with metastatic disease are usually best managed with chemo- therapy. Distant metastasis occurs in up to 10% of patients, with the lung being the most common site in 83% of cases.2 Systemic therapy can involve cytotoxic a Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Uni- versity School of Medicine, Baltimore, MD, USA; b Department of Hematology/Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA * Corresponding author.
    [Show full text]
  • ABVD Other Names: LYABVD
    For the Patient: ABVD Other names: LYABVD A Doxorubicin (also known as ADRIAMYCIN®) B Bleomycin V Vinblastine D Dacarbazine (also known as DTIC) Uses: • ABVD is a drug treatment given for Hodgkin's disease with the expectation of killing cancer cells. • ABVD is offered to patients with Hodgkin’s Lymphoma Treatment Plan: • Your treatment plan consists of several (up to 6) chemotherapy cycles. Each cycle lasts 4 weeks (=28 days). For each cycle, you will have two treatments given 2 weeks apart (Day 1 and Day 15). Each treatment consists of four chemotherapy drugs and a medicine called hydrocortisone (a steroid) injected into the vein. Two weeks after the second treatment (i.e. Day 29), you will start the next cycle. • The IV treatment takes about 3-4 hours. However, on Day 1 of each cycle, plan to spend part of that day at your treatment centre if you have a doctor’s appointment and a blood test. • Drugs: • Four chemotherapy drugs (doxorubicin, bleomycin, vinblastine, dacarbazine), and hydrocortisone are given as an IV injection in your arm on Day 1 and Day 15 of each cycle. • You take anti-nausea pills to help prevent nausea and vomiting. The anti- nausea prescription is filled at your drugstore. • During the course of your treatment, your cancer doctor may decide that you need a drug called filgrastim (also known as G-CSF, granulocyte colony stimulation factor) to improve your white blood cell count. If it is needed, the filgrastim is given as an injection under the skin (subcutaneous, SC) daily for 3 to 5 days, starting a few days after the chemotherapy (your doctor will specify when to start this).
    [Show full text]
  • Effective Treatment of Advanced Human Melanoma Metastasis In
    Published OnlineFirst July 21, 2009; DOI: 10.1158/1078-0432.CCR-08-3275 Published Online First on July 21, 2009 as 10.1158/1078-0432.CCR-08-3275 Cancer Therapy: Preclinical Effective Treatment of Advanced Human Melanoma Metastasis in Immunodeficient Mice Using Combination Metronomic Chemotherapy Regimens William Cruz-Munoz, Shan Man, and Robert S. Kerbel Abstract Purpose: The development of effective therapeutic approaches for treatment of meta- static melanoma remains an immense challenge. Present therapies offer minimal ben- efit. Although dacarbazine chemotherapy remains the standard therapy, it mediates only low response rates, usually of short duration, even when combined with other chemotherapeutic agents. Thus, new therapeutic strategies are urgently needed. Experimental Design: Using a newly developed preclinical model, we evaluated the ef- ficacy of various doublet metronomic combination chemotherapy against established advanced melanoma metastasis and compared these with the standard maximum tol- erated dose dacarbazine (alone or in combination with chemotherapeutic agents or vascular endothelial growth factor receptor–blocking antibody). Results: Whereas maximum tolerated dose dacarbazine therapy did not cause signifi- cant improvement in median survival, a doublet combination of low-dose metronomic vinblastine and low-dose metronomic cyclophosphamide induced a significant increase in survival with only minimal toxicity. Furthermore, we show that the incorpo- ration of the low-dose metronomic vinblastine/low-dose metronomic
    [Show full text]
  • CVD: Cisplatin, Vinblastine, and Dacarbazine
    PATIENT EDUCATION patienteducation.osumc.edu CVD: Cisplatin, Vinblastine, and Dacarbazine What is CVD? It is the short name for the drugs used in this chemotherapy treatment. The three drugs you will receive during this treatment are Cisplatin (“C”), Vinblastine (“V”), and Dacarbazine (DTIC-DomeTM or “D”). This chemotherapy will be given daily for 5 days. What is Cisplatin (SIS-pla-tin) and how does it work? Cisplatin is a chemotherapy drug known as an “alkylating agent.” Cisplatin works to stop fast growing cancer cells from dividing and making new cells. This will be given daily on days 2 through 5. What is Vinblastine (vin-BLAS-teen) and how does it work? Vinblastine is a chemotherapy drug known as an “anti-microtubule inhibitor.” This drug fights cancer cells by stopping fast growing cancer cells from dividing and making new cancer cells. This drug will be given daily on days 1 through 5. What is Dacarbazine (da-KAR-ba-zeen) and how does it work? Dacarbazine is a chemotherapy drug known as an “alkylating agent.” Dacarbazine works to stop fast growing cancer cells from dividing and making new cells. This drug will be given on the first day. This handout is for informational purposes only. Talk with your doctor or health care team if you have any questions about your care. © September 10, 2020. The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. Why am I getting three chemotherapy drugs for my cancer? These drugs work to stop fast growing cancer cells from dividing and making new cells, but they attack the cancer cells differently.
    [Show full text]
  • Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: a Case Series
    Brief Report Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series 1, 2, 1,2, Arielle Elkrief y, Suzanne Kazandjian y and Thierry Alcindor * 1 Cedars Cancer Center, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; [email protected] 2 Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; [email protected] * Correspondence: [email protected] These authors contributed equally to this paper. y Received: 7 December 2020; Accepted: 3 February 2021; Published: 5 February 2021 Abstract: Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively.
    [Show full text]
  • Efficacy, Safety, and Tolerability of Approved Combination BRAF and MEK Inhibitor Regimens for BRAF-Mutant Melanoma
    Cancers 2019, 11, 1642; doi:10.3390/cancers11111642 S1 of S5 Supplementary Materials: Efficacy, Safety, and Tolerability of Approved Combination BRAF and MEK Inhibitor Regimens for BRAF-Mutant Melanoma Omid Hamid, C. Lance Cowey, Michelle Offner, Mark Faries and Richard D. Carvajal Table S1. Anticancer Treatment by Regimen Following Study Drug Discontinuation. Dabrafenib + Trametinib Vemurafenib + Encorafenib + [1,2] Cobimetinib [3] Binimetinib [4] COMBI-v † COMBI-d coBRIM COLUMBUS n = 352 n = 209 n = 183 n = 192 Any treatment 72 (20%) 101 (48%) 105 (57%) 80 (42%) Immunotherapy NR 117 (56%) 67 (37%) NR Any anti–PD-1/anti–PD-L1 NR NR 28 (15%) 39 (20%) Ipilimumab (anti-CTLA-4) 41 (12%) 86 (41%) 53 (29%) 33 (17%) Nivolumab (anti-PD-1) NR 15 (7%) NR NR Pembrolizumab (anti–PD-L1) 4 (1%) 27 (13%) NR NR anti-CTLA-4 + NR NR 4 (2%) 6 (3%) anti–PD-1/anti–PD-L1 ‡ Targeted therapies NR 21 (10%) § 32 (18%) NR BRAFi + MEKi NR NR 15 (8%) 10 (5%) ¶ BRAFi NR NR 19 (10%) 11 (6%) # MEKi NR NR 2 (1%) NR Chemotherapy NR 37 (18%) 30 (16%) 14 (7%) ** Other NR NR 2 (1%) †† 5 (3%) ‡‡ NR = not reported. Data are n (%). PD-1 = programmed death cell receptor 1. PD-L1 = programmed death cell ligand 1. † Multiple uses of a type of therapy for an individual patient were only counted once in the frequency for that treatment category; patients mght have received multiple lines of treatment. Received by ≥2% of patients. ‡ Ipilimumab + nivolumab or ipilimumab + pembrolizumab. § Small-molecule targeted therapy.
    [Show full text]
  • Dacarbazine Medac 100 Mg (-200 Mg, -500 Mg, -1000 Mg) Summary of Product Characteristics 1. Name of the Medicinal Product Dacar
    medac GmbH 1.3.1.1.1 Document page: 1 Dacarbazine medac 100 mg (-200 mg, -500 mg, -1000 mg) Summary of Product Characteristics 1. Name of the Medicinal Product Dacarbazine medac 100 mg, Powder for solution for injection or infusion Dacarbazine medac 200 mg, Powder for solution for injection or infusion Dacarbazine medac 500 mg, Powder for solution for infusion Dacarbazine medac 1000 mg, Powder for solution for infusion 2. Qualitative and Quantitative Composition Each single-dose vial of Dacarbazine medac 100 mg (-200 mg, -500 mg, -1000 mg) contains 100 mg (200 mg, 500 mg, 1000 mg) dacarbazine (as dacarbazine citrate, formed in situ). After reconstitution Dacarbazine medac 100 mg (-200 mg) contains 10 mg/ml dacarbazine (see 6.6. a). After reconstitution and final dilution Dacarbazine medac 500 mg (-1000 mg) contains 1.4 – 2.0 mg/ml (2.8 – 4.0 mg/ml) dacarbazine (see 6.6. b). For excipients, see section 6.1. 3. Pharmaceutical Form Dacarbazine medac 100 mg (-200 mg): Powder for solution for injection or infusion. Dacarbazine medac 500 mg (-1000 mg): Powder for solution for infusion. Dacarbazine medac is a white or pale yellow powder. CLINICAL PARTICULARS 4.1 Therapeutic Indications Dacarbazine is indicated for the treatment of patients with metastasized malignant melanoma. Further indications for dacarbazine as part of a combination chemotherapy are: - advanced Hodgkin’s disease, - advanced adult soft tissue sarcomas (except mesothelioma, Kaposi sarcoma). 4.2 Posology and Method of Administration The use of dacarbazine should be confined to physicians experienced in oncology or hematology respectively. Dacarbazine is sensitive to light exposure.
    [Show full text]
  • Cancer Drug Costs for a Month of Treatment at Initial Food
    Cancer drug costs for a month of treatment at initial Food and Drug Administration approval Year of FDA Monthly Cost Monthly cost (2013 Generic name Brand name(s) approval (actual $'s) $'s) Vinblastine Velban 1965 $78 $575 Thioguanine, 6-TG Thioguanine Tabloid 1966 $17 $122 Hydroxyurea Hydrea 1967 $14 $97 Cytarabine Cytosar-U, Tarabine PFS 1969 $13 $82 Procarbazine Matulane 1969 $2 $13 Testolactone Teslac 1969 $179 $1,136 Mitotane Lysodren 1970 $134 $801 Plicamycin Mithracin 1970 $50 $299 Mitomycin C Mutamycin 1974 $5 $22 Dacarbazine DTIC-Dome 1975 $29 $125 Lomustine CeeNU 1976 $10 $41 Carmustine BiCNU, BCNU 1977 $33 $127 Tamoxifen citrate Nolvadex 1977 $44 $167 Cisplatin Platinol 1978 $125 $445 Estramustine Emcyt 1981 $420 $1,074 Streptozocin Zanosar 1982 $61 $147 Etoposide, VP-16 Vepesid 1983 $181 $422 Interferon alfa 2a Roferon A 1986 $742 $1,573 Daunorubicin, Daunomycin Cerubidine 1987 $533 $1,090 Doxorubicin Adriamycin 1987 $521 $1,066 Mitoxantrone Novantrone 1987 $477 $976 Ifosfamide IFEX 1988 $1,667 $3,274 Flutamide Eulexin 1989 $213 $399 Altretamine Hexalen 1990 $341 $606 Idarubicin Idamycin 1990 $227 $404 Levamisole Ergamisol 1990 $105 $187 Carboplatin Paraplatin 1991 $860 $1,467 Fludarabine phosphate Fludara 1991 $662 $1,129 Pamidronate Aredia 1991 $507 $865 Pentostatin Nipent 1991 $1,767 $3,015 Aldesleukin Proleukin 1992 $13,503 $22,364 Melphalan Alkeran 1992 $35 $58 Cladribine Leustatin, 2-CdA 1993 $764 $1,229 Asparaginase Elspar 1994 $694 $1,088 Paclitaxel Taxol 1994 $2,614 $4,099 Pegaspargase Oncaspar 1994 $3,006 $4,713
    [Show full text]
  • Injectable and Health Care Administered Oncology Medical Drug Criteria Through Preferred (Optional)
    Injectable and Health Care Administered Oncology Medical Drug Program Summary For patients with late stage metastatic disease (Stage IV), please refer to MP 2.373 Step Therapy Treatment in Cancer, Including Treatments for Stage Four, Advanced Metastatic Cancer and Severe Related Health Conditions for additional guidance *No Preferred Strategy The clinical rationale section is inf ormational, please refer to the medical drug criteria section for agents requiring medical drug review. FDA APPROVED INDICATIONS AND DOSAGE1-65 Agent Indication Dosage Abraxane® [paclitaxel ● Metastatic breast cancer Metastatic breast cancer: (protein bound)] af ter failure of combination 260 mg/m2 intravenously chemotherapy or relapse over 30 minutes, every 3 Injectable suspension within 6 months of adjuvant weeks chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated ● Locally advanced or NSCLC: metastatic Non-Small Cell 100 mg/m2 intravenously Lung Cancer (NSCLC) as over 30 minutes on Days 1, f irst-line treatment in 8, and 15 of each 21-day combination with cycle. Administer carboplatin, in patients who carboplatin on Day 1 of each are not candidates for 21-day cycle immediately curative surgery or radiation af ter Abraxane therapy ● Metastatic adenocarcinoma Metastatic of the pancreas as first-line adenocarcinoma of the treatment in combination pancreas: with gemcitabine 125 mg/m2 intravenously over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle. Administer gemcitabine immediately af ter paclitaxel (protein bound) on days 1, 8, and 15 of each 28-day cycle Adcetris® (brentuximab Treatment of adult patients vedotin) with: Injection for intravenous ● Previously untreated Stage Previously untreated use III or IV classical Hodgkin Stage III or IV cHL: 1.2 lymphoma (cHL) in mg/kg up to a maximum of combination with 120 mg every 2 weeks for a doxorubicin, vinblastine, and maximum of 12 doses dacarbazine CBC_CS_Reg_MDC_Injectable_and_Health_Care_Administered_Oncology_P rogSum_AR0620_r0321 Page 1 of 46 © Copyright Prime Therapeutics LLC.
    [Show full text]
  • Acronyms for Oncology Regimens
    ACRONYMS AND ABBREVIATIONS OF COMMONLY USED REGIMENS ACRONYM CHEMOTHERAPY COMBINATION 7 + 3 Anthracycline (daunorubicin/idarubicin) or anthracenedione (mitoxantrone)/cytarabine ABV Doxorubicin/ bleomycin/vincristine ABVD Doxorubicin/ bleomycin/vinblastine/dacarbazine AC Doxorubicin/cyclophosphamide ACE Doxorubicin/cyclophosphamide/etoposide AI Doxorubicin/ifosfamide AIDA Tretinoin/idarubicin/dexamethasone/mitoxantrone/6-mercaptopurine/ methotrexate AP Doxorubicin/cisplatin AT Doxorubicin/docetaxel BEACOPP Bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/ prednisone BEP Bleomycin/etoposide/cisplatin BMC Bleomycin/methotrexate/carmustine CAD Cyclophosphamide/doxorubicin/dacarbazine CAP Cyclophosphamide/doxorubicin/cisplatin CAPIRI Capecitabine/irinotecan CAPOX Capecitabine/oxaliplatin CAV Cyclophosphamide/doxorubicin/vincristine CDE Cyclophosphamide/doxorubicin/etoposide CDE-R Cyclophsopahmide/doxorubicin/etoposide/rituximab CECA Cyclophosphamide/etoposide/carboplatin/cytarabine CFAR Alemtuzumab/fludarabine/cyclophosphamide/rituximab CHOEP Cyclophosphamide/doxorubicin/vincristine/etoposide/prednisone CHOP Cyclophosphamide/doxorubicin/vincristine/prednisone CHOP-R Cyclophosphamide/doxorubicin/vincristine/prednisone/rtuximab ChlVPP Chlorambucil/vinblastine/procarbazine/prednisone CMF Cyclophosphamide/methotrexate/5-Fluorouracil CNOP Cyclophosphamide/mitoxantrone/vincristine/prednisone CODOX-M Cyclophsopahmide/vincristine/doxorubicin/cyclophosphamide/methotrexate/ leucovorin/intrathecal cytarabine/intrathecal methotrexate
    [Show full text]