DOCSLIB.ORG

Evaluation of Carboplatin Pharmacokinetics in the Absence and Presence of Paclitaxel’

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Evaluation of Carboplatin Pharmacokinetics in the Absence and Presence of Paclitaxel’ Vol. 2, 549-552, March 1996 Clinical Cancer Research 549 Evaluation of Carboplatin Pharmacokinetics in the Absence and Presence of Paclitaxel’ Coleman K. Obasaju, Steven W. Johnson, INTRODUCTION Andre Rogatko, Debbie Kilpatrick, Paclitaxel (Taxol) has demonstrated substantial activity as James M. Brennan, Thomas C. Hamilton, a single agent in the treatment of various solid tumors, including ovarian, breast, and lung cancers (1-6). Preclinical studies in- Robert F. Ozols, Peter J. O’Dwyer, dicated that the combination of Taxol and platinum compounds and James M. Gallo2 was superadditive in several models (1, 7, 8). The cellular basis Fox Chase Cancer Center, Philadelphia, Pennsylvania 191 1 1 for this favorable interaction has not yet been elucidated, but aspects of appropriate dosing strategies have been described in preclinical and early clinical studies. In MCF-7 breast cancer ABSTRACT and A549 lung cancer xenografts, the activity of simultaneous In a clinical trial of paclitaxel (Taxol) and carboplatin drug administration and that of the sequence Taxol preceding in combination, the severity of thrombocytopenia was less carbopiatin administration was superior to that of the reverse than would be expected with an equivalent dose of carbo- order (9). In a Phase I clinical trial of cispiatin and Taxol, more platin alone. To determine whether a pharmacokinetic in- severe neutropenia was associated with the sequence in which teraction was responsible for this observation, the effect of cisplatin was given first, and this sequence was associated with pretreatment with Taxol on the pharmacokinetics of carbo- a lower clearance of Taxol (10). The substantial clinical activity platin was examined in 1 1 patients. Each patient was ran- of the Taxol/cisplatin combination has been demonstrated in a domized to one of two treatment groups that determined the randomized trial in ovarian cancer ( 1 1 ), and studies in other order of drug treatments. The treatments were carboplatin diseases are in progress. as a 30-mm infusion alone or immediately following 175 Early clinical combination studies of Taxol with carbopla- mg/m2 Taxol administered as a 3-h i.v. infusion. The treat- tin lagged behind those with cisplatin because of concern re- ments were separated by 1 week. The carboplatin dose was garding additive myeiosuppression. In a Phase I trial in ovarian chosen to produce a target area under the concentration- cancer, in which the carboplatin dose was individualized ac- time curve (AUC) of 3.75 mg-mm/mi according to a previ- cording to the formula of Caivert et a!. (12), we found that full ously published formula (A. H. Calvert et a!., J. Clin Oncol., doses of each agent could be administered safely.3 Indeed, the 7: 1748-1756, 1989). The mean administered dose of carbo- severity of thrombocytopenia appeared to be even less than platin was 338 mg. Serial blood samples were collected over expected.3 The kinetics of both agents was characterized in that 24 h and analyzed for total and free platinum, and, in some study; although an initial impression suggested that carbopiatin patients, Taxol. The pharmacokinetics of carboplatin (i.e., AUC4 values were less than predicted, the analysis of the total clearance and volume of distribution at steady state), completed study demonstrated that the mean measured carbo- was not significantly affected by pretreatment with Taxol. platin AUC was 7.2 mg-mm/mI at a targeted AUC of 7.5 Total clearances of carbopiatin were 67.2 ± 28.8 ml/min and mg-min/ml.3 To determine more precisely whether the apparent 64.6 ± 27.9 mI/mm in the absence and presence of Taxol, alteration in platelet toxicity could be explained by a pharma- respectively (P 0.56). The AUC of free carboplatin (3.45 cokinetic interaction between Taxol and carboplatin, we de- mg-min/ml) obtained in the absence of Taxol was not signif- signed a study in which patients were treated both with carbo- icantly different from that measured in the presence of platin alone and with carboplatin following a 3-h infusion of Taxol (3.27 mg-min/ml). The AUC of carboplatin in both the Taxol. absence and presence of Taxol agreed with the projected target AUC of 3.75 mg-mm/mi. In conclusion, the applica- MATERIALS AND METHODS tion of an individualized dosing strategy is valid for the calculation of the carboplatin dose in this combination. The Study Design pharmacokinetics of carboplatin is not altered by pretreat- This trial was designed to test the effect of Taxol on ment with Taxol at a standard dose, and a pharmacokinetic carboplatin pharmacokinetics. Each patient received both car- interaction is not responsible for the altered toxicity of the combination. 3 M. A. Bookman, W. P. McGuire III, D. Kilpatrick, E. Keenan, W. M. Hogan, S. W. Johnson, P. J. O’Dwyer, E. Rowinsky, H. H. Gallion, and Received 8/1/95; revised 1 1/6/95; accepted 1 1/15/95. R. F. Ozols. Carboplatin and paxlitaxel in ovarian and peritoneal car- I Supported in part by NIH Grant CA-06972 and an appropriation from cinoma: a phase I study of the Gynecologic Oncology Group, submitted the Commonwealth of Pennsylvania. for publication. 2To whom requests for reprints should be addressed, at Fox Chase 4The abbreviations used are: AUC, area under the concentration-time Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111. curve; GFR, glomerular filtration rate; AUC24, partial area under the Phone: (215) 728-2461; Fax: (215) 728-2741. curve to 24 h; volume of distribution of steady state. Downloaded from clincancerres.aacrjournals.org on September 23, 2021. © 1996 American Association for Cancer Research. 550 Carboplatin Pharmacokinetics with Taxol boplatin alone and Taxol in combination with carboplatin. To Taxol Sampling minimize patient loss from the trial, the carboplatin dose was Two 8-ml blood samples were collected at the end of the split, and half administered in successive weeks. Patients re- Taxol infusion and at I 0 h from the start of infusion. Serum was ceived the Taxol before the first or second carboplatin dose by obtained from the blood samples and stored at - 80#{176}Cuntil random assignment. The end point of the study was the corn- analyzed for Taxol by a high-pressure liquid chromatography parison of the carbopiatin AUC and other pharmacokinetic assay. parameters with or without Taxol. Measurements of Carboplatin and Taxol Eligibility Criteria Total platinum in serum and ultrafiltrate platinum in serum The eligibility criteria included patients with histologically were measured with a flameless atomic absorption spectropho- confirmed malignant tumor for which treatment with Taxol and tometry. Samples were diluted in duplicate with 0.2% nitric acid carboplatin was appropriate therapy. Patients were required to containing 0.1% (v/v) Triton X-100 and injected (20 p.1) onto a have an Eastern Cooperative Oncology Group performance sta- Perkin Elmer/Cetus model 3 100 atomic absorption spectrometer tus 0-2, adequate bone marrow function (neutrophils 2000/ equipped with an HGA 600 graphite furnace. Platinum concen- mm3, platelet count I 00,000/mm3), renal function (creatinine trations were determined relative to a freshly prepared standard 2 mg/dl), and hepatic function (bilirubin 2 mg/dl). Pregnant curve for elemental platinum (0.2-4.0 ng). The limit of detec- or lactating women were excluded from the trial. Patients with tion was 0.01 p.g/ml (14). child-bearing potential had to implement adequate contraceptive A previously published high-pressure liquid chromatogra- measures during participation in this study. They had to be free phy method was used to quantitate Taxol in serum (15). In brief, of clinically significant infection and must have signed an a solid-phase extraction procedure was used to extract Taxol approved informed consent. from serum. Cephalomannine (final concentration 10 JaM) was used as an internal standard. Taxol was eluted from a C18 Treatment Plan Bond-Elut extraction column with acetonitrile. The acetonitrile Patients were randomized to one of two treatment groups. was evaporated, and the dried residue was reconstituted in 150 Group A. Patients received carbopiatin as a 30-mm i.v. p.1 mobile phase. The mobile phase consisted of 45% (v:v) 8 infusion at a dose calculated to produce a target AUC of 3.75 acetonitrile: water, pumped at 1 mi/mm through a Hypersil (100 mm X 4.6 mm) column. Taxol and internal standard were mg-mm/mi on day 1 . The dose was determined based on the detected at 230 nm, with a limit of quantitation of 15 ng/ml. formula of Calvert et al. (1 2): Dose (rng) = AUC (GFR + 25). This was followed on day 8 by the administration of 175 mg/rn2 Pharmacokinetic Analysis Taxol as a 3-h iv. infusion, followed immediately by carbopla- Pharmacokinetic analysis of carboplatin was conducted by tin at the same dose as on day 1 . GFR was estimated as (13): noncornpartmental analysis using the LAGRAN computer pro- gram (16). Cl1, and the terminal elimination half-life (t112) . (140 - age) weight GFR (ml/min) = . (22) in the absence and presence of Taxol were obtained using 72 (serum creatinine) standard formulas and examined for significant differences with paired t tests. A AUC24 was also obtained from the noncom- for males, and for females GFR is 0.85 times this formula. In partmental analysis and used for comparisons to the target AUC this formula, age is in years, weight in kgs, and serum creatinine of 3.75 mg-mm/mi. in mg/dl. Group B. Patients received the two treatments in reverse RESULTS order. Patient characteristics are shown in Table 1. A total of 13 All patients were premedicated with dexarnethasone (20 patients were accrued to the study; however, only 1 1 patients mg i.v or p.o.) 12 h, 6 h, and 1 h prior to Taxol.
Load more

Recommended publications
  • The Temperature-Dependent Effectiveness of Platinum-Based
    cells Article The Temperature-Dependent Effectiveness of Platinum-Based Drugs Mitomycin-C and 5-FU during Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Colorectal Cancer Cell Lines Roxan F.C.P.A. Helderman 1,2 , Daan R. Löke 2, Jan Verhoeff 3 , Hans M. Rodermond 1, Gregor G.W. van Bochove 1, Menno Boon 1, Sanne van Kesteren 1, Juan J. Garcia Vallejo 3, H. Petra Kok 2, Pieter J. Tanis 4 , Nicolaas A.P. Franken 1,2 , Johannes Crezee 2 and Arlene L. Oei 1,2,* 1 Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers (UMC), University of Amsterdam, Cancer Center Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands; [email protected] (R.F.C.P.A.H.); [email protected] (H.M.R.); [email protected] (G.G.W.v.B.); [email protected] (M.B.); [email protected] (S.v.K.); [email protected] (N.A.P.F.) 2 Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands; [email protected] (D.R.L.); [email protected] (H.P.K.); [email protected] (J.C.) 3 Department of Molecular Cell Biology & Immunology, Amsterdam Infection & Immunity Institute and Cancer Center Amsterdam, Amsterdam UMC, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands; j.verhoeff@amsterdamumc.nl (J.V.); [email protected] (J.J.G.V.) 4 Department for Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, P.O.
    [Show full text]
  • Arsenic Trioxide Is Highly Cytotoxic to Small Cell Lung Carcinoma Cells
    160 Arsenic trioxide is highly cytotoxic to small cell lung carcinoma cells 1 1 Helen M. Pettersson, Alexander Pietras, effect of As2O3 on SCLC growth, as suggested by an Matilda Munksgaard Persson,1 Jenny Karlsson,1 increase in neuroendocrine markers in cultured cells. [Mol Leif Johansson,2 Maria C. Shoshan,3 Cancer Ther 2009;8(1):160–70] and Sven Pa˚hlman1 1Center for Molecular Pathology, CREATE Health and 2Division of Introduction Pathology, Department of Laboratory Medicine, Lund University, 3 Lung cancer is the most frequent cause of cancer deaths University Hospital MAS, Malmo¨, Sweden; and Department of f Oncology-Pathology, Cancer Center Karolinska, Karolinska worldwide and results in 1 million deaths each year (1). Institute and Hospital, Stockholm, Sweden Despite novel treatment strategies, the 5-year survival rate of lung cancer patients is only f15%. Small cell lung carcinoma (SCLC) accounts for 15% to 20% of all lung Abstract cancers diagnosed and is a very aggressive malignancy Small cell lung carcinoma (SCLC) is an extremely with early metastatic spread (2). Despite an initially high aggressive form of cancer and current treatment protocols rate of response to chemotherapy, which currently com- are insufficient. SCLC have neuroendocrine characteristics bines a platinum-based drug with another cytotoxic drug and show phenotypical similarities to the childhood tumor (3, 4), relapses occur in the absolute majority of SCLC neuroblastoma. As multidrug-resistant neuroblastoma patients. At relapse, the efficacy of further chemotherapy is cells are highly sensitive to arsenic trioxide (As2O3) poor and the need for alternative treatments is obvious. in vitro and in vivo, we here studied the cytotoxic effects Arsenic-containing compounds have been used in tradi- of As2O3 on SCLC cells.
    [Show full text]
  • CARBOPLATIN- Carboplatin Injection Accord Healthcare, Inc
    CARBOPLATIN- carboplatin injection Accord Healthcare, Inc. --------- CARBOplatin Injection Rxo nly Carboplatin injection should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available. Bone marrow suppression is dose related and may be severe, resulting in infection and/or bleeding. Anemia may be cumulative and may require transfusion support. Vomiting is another frequent drug related side effect. Anaphylactic-like reactions to carboplatin have been reported and may occur within minutes of carboplatin injection administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms. DESCRIPTION Carboplatin injection is supplied as a sterile, pyrogen-free, 10 mg/mL aqueous solution of carboplatin, USP. Carboplatin, USP is a platinum coordination compound. The chemical name for carboplatin, USP is platinum, diammine [1,1-cyclobutanedicarboxylato(2-)-0,0']-,(SP-4-2), and carboplatin, USP has the following structural formula: C6H12N2O4Pt M.W. 371.25 Carboplatin, USP is a crystalline powder. It is soluble in water at a rate of approximately 14 mg/mL, and the pH of a 1% solution is 5 to 7. It is virtually insoluble in ethanol, acetone, and dimethylacetamide. CLINICAL PHARMACOLOGY Carboplatin, like cisplatin, produces predominantly interstrand DNA cross-links rather than DNA-protein cross-links. This effect is apparently cell-cycle nonspecific. The aquation of 2 carboplatin, which is thought to produce the active species, occurs at a slower rate than in the case of cisplatin. Despite this difference, it appears that both carboplatin and cisplatin induce equal numbers of drug-DNA cross-links, causing equivalent lesions and biological effects.
    [Show full text]
  • BC Cancer Protocol Summary for Neoadjuvant Or Adjuvant Therapy for Breast Cancer Using Docetaxel, Carboplatin, and Trastuzumab
    BC Cancer Protocol Summary for Neoadjuvant or Adjuvant Therapy for Breast Cancer Using DOCEtaxel, CARBOplatin, and Trastuzumab Protocol Code BRAJDCARBT Tumour Group Breast Contact Physician Dr. Susan Ellard ELIGIBILITY: . ECOG 0-1 . Node positive or high risk node negative, including patient with T1b disease (T1a still requires CAP approval) . HER-2 over-expression defined as either IHC3+, or FISH amplification ratio greater than or equal to 2 per BC Cancer central laboratory . Adequate renal and hepatic function . Adequate hematological parameters (ANC greater than 1.5 x 109/L and platelets greater than 100 x 109/L) . No signs or symptoms of cardiac disease. LVEF greater than or equal to 50%* * If the LVEF is between 45-50%, the oncologist may decide to treat based on clinical assessment EXCLUSIONS: . ECOG 2-4 . Stage IV disease (please refer to advanced regimens) . Significant hepatic dysfunction, contraindicating DOCEtaxel . Significant cardiovascular disease and/or LVEF less than 50%; if initial reading is less than 50%, physician may consider repeating for validity, or assessing LVEF by the other modality, e.g. echocardiogram instead of MUGA . greater than or equal to grade 2 sensory or motor neuropathy . Pregnancy or lactation TESTS: . Baseline: CBC & diff, platelets, bilirubin, GGT, ALT, LDH, alkaline phosphatase, creatinine, (see Precaution #5 for guidelines regarding hepatic dysfunction and DOCEtaxel), suggested: nuclear renogram for GFR (if available locally, and not previously done) . Before each treatment cycle: CBC & diff, platelets, creatinine . MUGA scan or echocardiogram: prior to first treatment with trastuzumab and every 3-4 months until completion of treatment per the discretion of the treating physician.
    [Show full text]
  • Chemotherapy Protocol LUNG CANCER – SMALL CELL (SCLC) CARBOPLATIN (AUC6)-ETOPOSIDE (Intravenous / Oral) Regimen SCLC – Carbo
    Chemotherapy Protocol LUNG CANCER – SMALL CELL (SCLC) CARBOPLATIN (AUC6)-ETOPOSIDE (Intravenous / Oral) Regimen SCLC – Carboplatin (AUC6)-Etoposide IV/PO Indication First line treatment of SCLC WHO Performance status 0, 1, 2, 3 Toxicity Drug Adverse Effect Carboplatin Neuropathy, hypersensitivity Etoposide Hypotension on rapid infusion, hyperbilirubinaemia The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Disease A baseline chest x-ray should be performed before starting treatment and up to date (ideally within 1 month) cross section imaging should also be performed Regimen EDTA or calculated creatinine clearance before the 1st cycle. FBC, LFTs and U&Es prior to each cycle A chest x-ray should be performed before each cycle Dose Modifications The dose modifications listed are for haematological, liver and renal function only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re- escalated in subsequent cycles without consultant approval. It is also a general rule Version 1.3 (December 2013) Page 1 of 7 SCLC- Carboplatin (AUC6)-Etoposide IV/PO for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. The following is a general guide only. Haematology Prior to prescribing on day one of cycle one the following criteria must be met; Criteria Eligible Level Neutrophil equal to or more than 1.5x109/L Platelets equal to or more than 100x109/L Consider blood transfusion if patient symptomatic of anaemia or haemoglobin of less than 8g/dL Subsequently if the neutrophils are less than 1x109/L then in the first instance delay treatment for seven days.
    [Show full text]
  • Stability of Carboplatin and Oxaliplatin in Their Infusion Solutions Is Due to Self-Association
    Syracuse University SURFACE Chemistry - Faculty Scholarship College of Arts and Sciences 2011 Stability of Carboplatin and Oxaliplatin in their Infusion Solutions is Due to Self-Association Anthony J. Di Pasqua Syracuse University Deborah J. Kerwood Syracuse University Yi Shi Syracuse University Jerry Goodisman Syracuse University James C. Dabrowiak Syracuse University Follow this and additional works at: https://surface.syr.edu/che Part of the Chemistry Commons Recommended Citation Di Pasqua, Anthony J.; Kerwood, Deborah J.; Shi, Yi; Goodisman, Jerry; and Dabrowiak, James C., "Stability of Carboplatin and Oxaliplatin in their Infusion Solutions is Due to Self-Association" (2011). Chemistry - Faculty Scholarship. 29. https://surface.syr.edu/che/29 This Article is brought to you for free and open access by the College of Arts and Sciences at SURFACE. It has been accepted for inclusion in Chemistry - Faculty Scholarship by an authorized administrator of SURFACE. For more information, please contact [email protected]. View Article Online / Journal Homepage / Table of Contents for this issue Dalton Dynamic Article Links Transactions Cite this: Dalton Trans., 2011, 40, 4821 www.rsc.org/dalton COMMUNICATION Stability of carboplatin and oxaliplatin in their infusion solutions is due to self-association Anthony J. Di Pasqua,† Deborah J. Kerwood, Yi Shi, Jerry Goodisman and James C. Dabrowiak* Received 13th December 2010, Accepted 23rd March 2011 DOI: 10.1039/c0dt01758b Carboplatin and oxaliplatin are commonly used platinum anticancer agents that are sold as ready-to-use aqueous infusion solutions with shelf lives of 2 and 3 years, respectively. The observed rate constants for the hydrolysis of these drugs, however, are too large to account for their long shelf lives.
    [Show full text]
  • Carboplatin /Etoposide (Oral & IV Regimens)
    THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST Systemic Anti-Cancer Treatment Protocol Carboplatin / Etoposide (Oral and IV regimens) PROTOCOL REF: MPHACAETLU (Version No: 1.0) Approved for use in Small cell lung cancer Small cell cancer – any origin Dosage Drug Dose Route Frequency Carboplatin AUC 5 x (GFR + 25) IV infusion Day 1 only Etoposide phosphate 100mg/m2 IV Day 1 only Etoposide 200mg/m2 PO in 2 divided doses Days 2 and 3 Alternatively IV Days 2 and 3 100mg/m2 Repeated every 3 weeks for up to 6 cycles Calvert formula for Carboplatin dosage Carboplatin dose in mg = AUC x (creatinine clearance + 25) If estimated GFR is used the Wright formula must be used for creatinine clearance. Do not use Cockcroft and Gault formulae as it is less accurate. Supportive Treatments Anti-emetic risk - Moderate Dexamethasone tablets, 4mg twice daily for 3 days Domperidone 10mg oral tablets, up to 3 times a day as required Issue Date: October 2017 Review Date: October 2021 Page 1 of 6 Protocol reference: MPHACAETLU Author: Tara Callagy Authorised by: Dr Carles Escriu & DTC Version No: 1.0 THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST Interactions Aminoglycosides e.g. gentamicin, vancomycin and diuretics Increased risk of nephrotoxicity and ototoxicity. Renal function should be well monitored and audiometric tests carried out as indicated. Phenytoin Carboplatin can cause a decrease in phenytoin serum levels. This may lead to reappearance of seizures and may require an increase of phenytoin dosages. Warfarin The effects of warfarin may
    [Show full text]
  • Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx )
    Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx®) DRUG ADMINISTRATION SCHEDULE Day Drug Dose Route Diluent Rate Fast 5% Glucose 250/500ml Infusion Running Dexamethasone 8mg Oral Ondansetron* 8mg Oral /Slow bolus/15 min infusion Day 1 Liposomal 250ml 30 mg/m2 Infusion See below DOXOrubicin (Caelyx®) 5% Glucose 250ml CARBOplatin AUC 5 IV infusion 30 mins 5% Glucose *Ondansetron IV must be infused over 15 minutes in patients over 65 years of age. CARBOPLATIN DOSAGE: Dose (mg) = AUC x (GFR + 25) Where the GFR is the non-corrected EDTA clearance. If estimated GFR is undertaken the Wright formula must be used with AUC 5. Cockcroft & Gault formula is less accurate. INFUSION RATE The first dose of Caelyx® is administered at a rate no greater than 1 mg/minute. If no infusion reaction is observed, subsequent Caelyx® infusions may be administered over a 60-minute period. CYCLE LENGTH AND NUMBER OF DAYS Every four weeks until disease progression APPROVED INDICATIONS Second-line (or subsequent) treatment of patients with partially platinum-sensitive, platinum- resistant or platinum-refractory advanced ovarian cancer. ELIGIBILITY CRITERIA ECOG performance status 0 to 2 EXCLUSION CRITERIA In patients who have severe bone marrow depression and/or severe renal or severe hepatic impairment PREMEDICATION Antiemetic cover with neurokinin 1 (NK1) receptor antagonists ASCO 2017 antiemetic guidance recommends regimens containing carboplatin ≥ AUC4 should be classified as high risk of CINV and patients offered a three-drug combination of a neurokinin 1 (NK1) receptor antagonist, a serotonin (5-HT3) receptor antagonist and dexamethasone. Current practice in NCA is to start with a two-drug regimen serotonin (5-HT3) receptor antagonist and dexamethasone and add in a neurokinin 1 (NK1) receptor antagonist if CINV not adequately controlled.
    [Show full text]
  • Combination Chemotherapy with Estramustine Phosphate, Ifosfamide and Cisplatin for Hormone-Refractory Prostate Cancer
    Acta Med. Okayama, 2006 Vol. 60, No. 1, pp. 43ﾝ49 CopyrightⒸ 2006 by Okayama University Medical School. Original Article http ://www.lib.okayama-u.ac.jp/www/acta/ Combination Chemotherapy with Estramustine Phosphate, Ifosfamide and Cisplatin for Hormone-refractory Prostate Cancer Haruki Kakua, Takashi Saikaa＊, Tomoyasu Tsushimab, Atsushi Nagaia, Teruhiko Yokoyamaa, Fernando Abarzuaa, Shin Ebaraa, Daisuke Manabea, Yasutomo Nasua, and Hiromi Kumona aDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700ﾝ8558, Japan, and bDepartment of Urology, Medival center of Okayama, Okayama 701-1192, Japan We evaluated the effi ciency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cis- platin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no eff ective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50ｵ reduc- tion in prostate-specifi c antigen was observed in 9 of 18 patients (50ｵ), and a more than 50ｵ reduc- tion in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29ｵ). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC.
    [Show full text]
  • New Strategies Against Prostate Cancer – Pt(II)-Based Chemotherapy
    Send Orders of Reprints at [email protected] 4678 Current Medicinal Chemistry, 2012, 19, 4678-4687 New Strategies Against Prostate Cancer – Pt(II)-Based Chemotherapy C.S. Matos1, A.L.M.B. de Carvalho1, R.P. Lopes1 and M.P.M. Marques*,1,2 1Research Unit “Molecular Physical Chemistry”, University of Coimbra – Portugal; 2Departament of Life Sciences, Faculty of Sci- ence and Technology, University of Coimbra – Portugal Abstract: Prostate cancer is the second most common cancer worldwide and the sixth cause of cancer-related death in men. When hor- mone therapy fails to control tumour growth, castration-resistant prostate cancer (CRPC) occurs and chemotherapy drugs must be admin- istered. Since 2004, docetaxel administration is the standard of care in metastatic CRPC, although it presents severe limitations such as acquired resistance and poor prognosis. An analogue (cabazitaxel) was approved by the FDA in 2010 as a second-line chemotherapeutic agent. Novel immuno- and hormonal therapy agents, as well as tumour vaccines, have been recently developed, but new strategies are still needed for effectively handling this type of neoplasia. Platinum compounds, in particular, have been the object of a growing interest, despite the former belief that they should have modest activity against prostate cancer. Compounds such as carboplatin, oxaliplatin or sa- traplatin, either alone or in combination, have lately shown promising results. In order to overcome the deleterious side-effects usually associated to these metal-based agents, several approaches have been followed with a view to optimise drug delivery and targeting, some of which showed considerable success in CRPC. Platinum drugs may therefore have an important role in the chemotherapeutic manage- ment of human metastatic castration-resistant prostate cancer, mostly in second-line strategies.
    [Show full text]
  • Carboplatin(AUC2)-Paclitaxel RT
    Chemotherapy Protocol GASTROINTESTINAL (UPPER) CANCER CARBOPLATIN (AUC2)-PACLITAXEL-RADIOTHERAPY Regimen • Gastrointestinal (Upper) Cancer – Carboplatin(AUC2)-Paclitaxel-Radiotherapy Indication • Neoadjuvant treatment of resectable cancer of the oesophagus or oesophagogastric junction • WHO performance status 0, 1, 2 Toxicity Drug Adverse Effect Thrombocytopenia, peripheral neuropathy, nephrotoxicity at high Carboplatin doses, electrolyte disturbances Hypersensitivity, hypotension, bradycardia, peripheral Paclitaxel neuropathy, myalgia and back pain on administration The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Drugs • FBC, LFTs and U&Es prior to each day of treatment • EDTA or calculated creatinine clearance before each treatment Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Version 1.2 (October 2020) Page 1 of 8 GI (Upper) – Carboplatin (AUC2)-Paclitaxel RT Haematological Dose modifications for haematological toxicity in the table below are for general guidance only. Always refer to the responsible consultant as any dose reductions or delays will be dependent on clinical circumstances and treatment intent. Consider blood transfusion if patient symptomatic of anaemia or has a haemoglobin of less than 8g/dL.
    [Show full text]
  • Lung Pathway Group – Docetaxel & Carboplatin in Non- Small Cell Lung Cancer (NSCLC)
    Lung Pathway Group – Docetaxel & Carboplatin in Non- Small Cell Lung Cancer (NSCLC) Indication: First line palliative therapy for previously untreated Stage IIIB or IV NSCLC patients Regimen details: Docetaxel 75 mg/m2 IV Day 1 Carboplatin AUC 5 (EDTA) IV Day 1 Administration: Docetaxel in 250ml or 500ml Sodium Chloride 0.9% depending on final concentration IV over 1 hour Carboplatin in 500ml Glucose 5% IV over 30 to 60 minutes Aluminium containing equipment should not be used during preparation and administration of carboplatin Hypersensitivity reactions may occur, such as flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills, usually during the first and second infusions and within a few minutes following the start of the infusion; the infusion should be slowed down or interrupted and the necessary supportive medication should be administered. Severe reactions such as hypotension and/or bronchospasm or generalised rash/erythema requires immediate discontinuation. Availability of resuscitation equipment must be ensured as a standard precaution. Frequency: Day 1, every 21 days, for 4 to 6 cycles Pre-medication: Oral dexamethasone 8mg BD for 3 days, starting the day before docetaxel administration to reduce the incidence and severity of fluid retention and hypersensitivity reactions. If the patient has not taken the oral premedication, clinicians may prescribe dexamethasone IV 20mg, chlorphenamine IV 10mg and ranitidine IV 50mg to be administered 1 hour prior to chemotherapy. Version: 1.0 Supersedes:
    [Show full text]