DOCSLIB.ORG

Carboplatin /Etoposide (Oral & IV Regimens)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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 be increased. Monitor INR closely. Extravasation risk Carboplatin: Irritant Etoposide phosphate: Non vesicant Refer to the network guidance for the prevention and management of extravasation Administration Day Drug Dose Route Diluent and rate 1 Dexamethasone 8mg PO 30 mins before chemotherapy Ondansetron 16mg PO 30 mins before chemotherapy Carboplatin AUC 5 IV In 500mL glucose 5% over 30 to 60 minutes Etoposide phosphate 100mg/m2 IV In 100mL sodium chloride 0.9% infusion over 15 minutes 2 Etoposide capsules 200mg/m2 PO in 2 divided doses 3 Etoposide capsules 200mg/m2 PO in 2 divided doses OR Issue Date: October 2017 Review Date: October 2021 Page 2 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 For patients who are unable to swallow etoposide capsules Day Drug Dose Route Diluent and rate 2 Etoposide phosphate 100mg/m2 IV In 100mL sodium chloride 0.9% infusion over 15 minutes 3 Etoposide phosphate 100mg/m2 IV In 100mL sodium chloride 0.9% infusion over 15 minutes If etoposide phosphate is unavailable then switch to standard etoposide intravenous preparation, administered in 250mL to 1000mL of sodium chloride 0.9% (concentration dependent expiry) over 60 minutes. Notes Carboplatin Facilities to treat anaphylaxis must be present when administering carboplatin. If a patient experiences an infusion-related reaction, give future does with pre-medication cover of IV chlorphenamine 10mg and IV hydrocortisone 100mg. Risk of infusion related reaction may be increased with previous exposure to platinums Etoposide Round oral etoposide doses to the nearest 50mg Swallow whole on an empty stomach or one hour before food Main Toxicities Nausea, vomiting, myelosuppression (thrombocytopenia, anaemia and neutropenia), alopecia Carboplatin – nephrotoxicity, ototoxicity, infusion related reactions, transient liver enzyme increase Issue Date: October 2017 Review Date: October 2021 Page 3 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 Etoposide – mucositis, oesophagitis and stomatitis occur infrequently, hyper or hypotension – see below, fatigue, fever, bronchospasm, peripheral neuropathy Investigations and treatment plan Pre Cycle 1 Cycle 2 Cycle 3 Cycle 4 Ongoing Medical X X X Alternate cycles Assessment Nursing X X X X X Every cycle Assessment FBC X X X X X Every cycle U&E & LFT & X X X X X Every cycle Mg Mg and Ca x X x x x Every cycle Serum Cr X X X X X Every cycle CrCl (Wright) X X X X Every cycle CT scan X X At end of treatment Informed X Consent Repeat as ECG X clinically indicated Blood Repeat if clinically X pressure indicated Respiratory Rate and O2 X X X X X Every cycle sats PS recorded X X X X X Every cycle Toxicities X X X X X Every cycle documented Weight X X X X X Every cycle recorded Blood Repeat if clinically X Glucose indicated Issue Date: October 2017 Review Date: October 2021 Page 4 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 Dose Modifications and Toxicity Management Haematological Toxicity Proceed on day 1 if- Plt ≥ 100 x 109/L ANC ≥ 1.0 x 109/L Delay 1 week on day 1 if- Plt ≤ 99 x 109/L ANC ≤ 0.9 x 109/L These haematological guidelines assume that patients are well with good performance status, that other acute toxicities have resolved and the patient has not had a previous episode of neutropenic sepsis. Non Haematological Toxicity Renal Carboplatin Measure serum creatinine every cycle and use the Wright Formula to calculate CrCl. Note limitations of Wright Formula for very high and low CrCl. Discuss with consultant if in doubt.Patients with creatinine clearance values of less than 60 ml/min are at greater risk to develop myelosuppression. Carboplatin is contraindicated if glomerular filtration rate is ≤ 20 ml/min. Do not give carboplatin and discuss with Oncologist The optimal use of carboplatin in patients presenting with impaired renal function requires adequate dosage adjustments and frequent monitoring of both haematological nadirs and renal function. Etoposide CrCl (mL/min) Etoposide Dose Above 50 100% 15 to 50 75% Below 15 50% Issue Date: October 2017 Review Date: October 2021 Page 5 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 Hepatic Carboplatin- Transient increases in liver enzymes have been reported. Probably no dose reduction necessary. Etoposide – conflicting information exists for reductions with etoposide, use table below but discuss with oncologist if in doubt Bilirubin (μmol/L) AST/ALT Etoposide Dose (units/L) 26 to 51 or 60 to 180 50% Above 51 or >180 Clinical decision Infusion These can occur with carboplatin and rarely with etoposide. Hypotension related can occur if etoposide is administered too quickly – slower the infusion and reactions give subsequent infusions at the slower rate Hypertension and flushing can also occur – stop infusion, monitor; blood pressure usually reverts to normal after a few hours References Carboplatin Summary of Product Characteristics, Hospira UK Ltd, Warwickshire. 20/07/05. Available from www.medicines.org.uk/emc/medicine. last updated 09/06/2009. Etopophos 100mg Powder for Solution for Injection, Summary of Product Characteristics Bristol-Myers Squibb Pharmaceutical Limited.23/05/1996 Available from www.medicines.org.uk/emc/medicine. Last updated 17/02/2012. Dosage Adjustment for Cytotoxics in Hepatic Impairment. January 2009 UCLH - Dosage Adjustment for Cytotoxics in Hepatic Impairment (Version 3 - updated January 2009) Dosage Adjustment for Cytotoxics in Renal Impairment. January 2009 UCLH - Dosage Adjustment for Cytotoxics in Renal Impairment (Version 3 - updated January 2009) Dooly M, Poole S, Limitations of Wright Formula estimates of renal function, Ann Oncol (June 2005) 16(6) 989-990 Issue Date: October 2017 Review Date: October 2021 Page 6 of 6 Protocol reference: MPHACAETLU Author: Tara Callagy Authorised by: Dr Carles Escriu & DTC Version No: 1.0 .
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 & 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]
  • Drug Discovery, Volume 2, Number 6, December 2012 FDA APPROVED DRUGS 396 5 – DRUG DISCOVERY EISSN 2278 0X 54 – ISSN 2278 FDA Approved Drugs - October 2012
    FDA APPROVED DRUGS Drug discovery, Volume 2, Number 6, December 2012 FDA APPROVED DRUGS 396 5 – DRUG DISCOVERY EISSN 2278 0X 54 – ISSN 2278 FDA approved drugs - October 2012 Brithvi V Department of Pharmaceutical Technology, Anna University, BIT Campus, Trichy, Tamil Nadu, India Correspondence to: Department of Pharmaceutical Technology, Anna University, BIT Campus, Trichy, Tamil Nadu, India, E-mail: [email protected] 1. SYNRIBO (OMACETAXINE MEPESUCCINATE) 1.1. Company Teva Pharmaceuticals; Approved by October 2012 1.2. Treatment Area Chronic or accelerated phase chronic myeloid leukemia 1.3. General Information Synribo (omacetaxine mepesuccinate) is a cephalotaxine ester. It is specifically approved for the treatment of adults with chronic or accelerated phase chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. It is supplied as a solution for subcutaneous administration. The recommended dosage is 1.25 mg/m2 administered subcutaneously twice daily for 7 consecutive days every 28 days, over a 28-day cycle. Treatment should continue as long as patients are clinically benefiting from therapy. 1.4. Mechanism of Action Synribo (omacetaxine mepesuccinate) is a protein synthesis inhibitor and is independent of direct Bcr-Abl binding. Omacetaxine mepesuccinate binds to the A-site cleft in the peptidyl-transferase center of the large ribosomal subunit from a strain of archaeabacteria. In vitro, omacetaxine mepesuccinate reduced protein levels of the Bcr-Abl oncoprotein and Mcl-1, an anti-apoptotic Bcl-2 family member. 1.5. Side Effects Adverse events associated with the use of Synribo include: Thrombocytopenia, anemia , neutropenia , diarrhea , nausea , fatigue , asthenia , injection site reaction , pyrexia , infection , lymphopenia 2.
    [Show full text]