Docetaxel toxicity

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

Docetaxel asthenia, peripheral neuropathy, alopecia, cardiovascular Fatigue, nausea, vomiting, skin toxicity, neuropathy, anemia, Mild (on administration days... 

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. 

Other suggested mechanisms for the increased radiosensitization seen with both paclitaxel and docetaxel include an increased alpha component of DNA damage and the fact that docetaxel is toxic for S-phase cells that are maximally radiation resistant (41,42). 

Koukourakis MI, Giatromanolaki A, SchizaS, Kakolyris S,Georgoulias V. Concurrenttwice-a-week docetaxel and radiotherapy a dose escalation trial with immunological toxicity evaluation. Int JRadiat Oncol Biol Phys 1999 43(1) 107-114. 

As a single agent in the setting of locoregional, recurrent, and metastatic disease, docetaxel is also tolerated fairly well with leukopenia as the primary dose-limiting toxicity (39). Response rates have been favorable at approx 42% when administered docetaxel (100 mg/m2) every 21 d. Hesse et al. reported on significant toxicides encountered in a phase I study of concomitant taxotere (initial dose = 15 mg/m2)/conventional radiation therapy (70 Gy) grade 3/4 radiation dermatitis, neuropathy, and thrombocytopenia at dose level 1 (40). Of five evaluable patients three patients achieved a CR and one patient achieved a PR. Based on the severity of these toxicities, this treatment schedule was not pursued further. 

Docetaxel is a semisynthetic taxane derived from the European yew tree. Its mechanism of action, metabolism, and elimination are identical to those of paclitaxel. It is approved for use as second-line therapy in advanced breast cancer and non-small cell lung cancer, and it also has major activity in head and neck cancer, small cell lung cancer, gastric cancer, advanced platinum-refractory ovarian cancer, and bladder cancer. Its major toxicities are listed in Table 54-4. 

Outline the specific toxicities associated with trastuzumab and docetaxel therapy, including any longer term complications. 

Many clinicians now prefer to use docetaxel (licensed to be used in combination with trastuzumab for metastatic breast cancer) instead of paclitaxel as it is more convenient to administer (1 hour infusion for docetaxel instead of 3 hours for paclitaxel) and clinicians generally have more experience of using this agent in breast cancer therapy. The pivotal trial of this combination shows superiority of docetaxel and trastuzumab over docetaxel alone in terms of overall survival, response rate and time to disease progression with little additional toxicity (Marty etal., 2005). 

Taxine alkaloids are complex polycyclic compounds in which N is present but not as an integral part of a ring. The taxines are found in Taxus (yew) species (Taxaceae). Taxine A (C61 CIO ] C6-0-C0-CH(0H)-CH(N(CH3)2)-Phe) is substantially responsible for yew toxicity. The related polycyclic amide taxol (paclitaxel) and the closely related docetaxel are tubulin-binding, antimitotic cytotoxics that are used clinically as anticancer drugs. A variety of taxines have been isolated from Taxus species. 

DOCETAXEL ANTIBIOTICS -ERYTHROMYCIN t docetaxel levels Inhibition of CYP3A4-mediated metabolism of docetaxel is metabolized by enzymes that are moderately inhibited by erythromycin, leading to t levels and possible toxicity Cautious use, or consider use of azithromycin, which has little effect on CYP3A4 and is therefore not expected to interact with docetaxel... 

DOCETAXEL CICLOSPORIN T plasma concentrations of these drugs, with risk of toxic effects Competitive inhibition of CYP3A4-mediated metabolism and P-gp transport of these drugs Watch for toxic effects of these drugs... 

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