Docetaxel Cisplatin

Cisplatin-docetaxel diarrhea, cardiac toxicity, renal toxicity, neuropathy, weakness, hypersensitivity reactions, anemia Infection, thromocytopenia, nausea, vomiting, diarrhea, cardiac, High (day 1 only)... 

CISPLATIN DOCETAXEL t docetaxel levels, with t risk of profound myelosuppression. Concurrent use also t risk of neurotoxicity 1 clearance of docetaxel when docetaxel is administered after cisplatin Administer docetaxel first and follow with cisplatin... 

Four to six cycles of doublet chemotherapy with cisplatin or carboplatin plus docetaxel, gemcitabine, paclitaxel, or vinorelbine are recommended as first-line chemotherapy for patients with unresectable stage III or IV NSCLC. No combination was found to be superior tolerance of expected toxicities may contribute to the decision. 

Etoposide/cisplatin Vinorelbine/gemcitabine Paclitaxel/gemcitabine Gemcita bi ne/ docetaxel Paclitaxel/vinorelbine... 

Isla, D., Sarries, C., Rosell, R., et al. (2004) Single nncleofide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-smaU-ceU lung cancer. Ann. Oncol. 15,1194-1203. 

Segawa Y, Ueoka H, Kiura K, et al. A phase I/II study of docetaxel (TXT) and cisplatin (CDDP) with concurrent thoracic radiotherapy (TRT) for locally advanced non-small-cell lung cancer (LA-NSCLC). ProcAm Soc Clin Oncol 2000 19 508a. 

Nyman J, Mercke C. Accelerated radiotherapy with docetaxel and cisplatin as induction and concomitant chemotherapy for stage III non-small cell lung cancer. Lung Cancer 2000 29(Suppl 1) 98. 

Colevas AD, Busse PM, Norris CM, et al. Induction chemotherapy with docetaxel, cisplatin, fluorou-racil, and leuco vorin for squamous cell carcinoma of the head and neck a phase I/II trial. J Clin Oncol 1998 16(4) 1331—1339. 

Posner MR, Glisson B, FrenetteG, etal. Multicenter phase I-II trial of docetaxel, cisplatin, and fluorouracil induction chemotherapy for patients with locally advanced squamous cell cancer of the head and neck. J Clin Oncol 2001 19 1096-1104. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Investigators found that human breast cancer cell lines with BRCAl mutations showed a twofold to fourfold increase in apoptosis after treatment with ionizing radiation, cisplatin, or doxorubicin, compared with cells free of mutations. They also found that BRCAl tumor cell lines were resistant to other agents, such as paclitaxel (Taxol) and docetaxel (Taxotere), treatments used commonly in ovarian cancer and advanced-stage breast cancers. 

Our laboratories were the first to use CEPH family cell lines to demonstrate that a significant genetic component contributed to susceptibility to the cytotoxic effects of cisplatin, 5-FU and docetaxel (17,18). Dolan et al. estimated the heritability for susceptibility to cisplatin-induced cytotoxicity to be approximately 0.47 therefore sensitivity to the C5dotoxic effects of cisplatin is under appreciable genetic influence. Linkage analysis was performed and the strongest signal (lod 2.16, empirical /7-value 0.0005) was found on chromosome 1 at 44 cM (18). 

BRCAi A Potential Predictive Marker for CiSPLATIN AND DOCETAXEL BRCAi IN THE Transcriptional Regulation OF Spindle Checkpoint Genes Clinical Trials of Customized Chemotherapy References... 

This study shows that assessment of ERCC 1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel plus cisplatin. Further studies are warranted to optimize methodologies for ERCCI analysis in small tumor samples and to refine a multi-biomarker profile predictive of patient outcome. Other... 

Fig. 5. Diagram of a potential customized chemotherapy trial based on the expression of NER-related genes. Patients with low levels of BRCAl expression (Ql) are assigned to receive gem-citabine/cisplatin patients with intermediate levels of BRCAl expression (Q2 3) will receive docetaxel/cisplatin patients with high levels of BRCAl expression will receive docetaxel alone.

Larotaxel (XRP-9881, RPR 109881A) 59 (Sanofi-Aventis) is undergoing Phase III trials in patients with advanced pancreatic cancer who had been previously treated with gemcitabine, as well as in combination with cisplatin to treat locally advanced/metastatic urothelial tract or bladder cancer.124 A Phase III trial for the treatment of advanced breast cancer has been completed. Larotaxel 59129>130 js a semi-synthetic derivative of 10-deacetyl baccatin III with a docetaxel-like side chain that has a low affinity for the P-glycoprotein drug efflux pump, an efflux mechanism that diminishes the effectiveness of the marketed drugs paclitaxel 60 and docetaxel. Importantly, this low affinity should enable larotaxel 59 to be effective in tumours resistant to paclitaxel 60... 

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