Chemotherapy taxanes

Approximately 50% to 60% of women who have not received prior chemotherapy for metastatic disease will respond to chemotherapy regimens doxorubicin- and taxane-containing regimens are the most active. 

The taxanes (e.g., paclitaxel and docetaxel) are a newer class of agents that rival the anthracyclines in their activity in metastatic breast cancer, becoming (arguably) the most active class of chemotherapy for this disease. 

In patients with bulky disease or a significant tumor burden, neoadjuvant chemotherapy can be used to decrease tumor burden to increase the likelihood of optimal tumor debulking during surgery.35 Typically, three cycles of the standard combination taxane/platinum regimen is administered once every 3 weeks. After surgery, the patient will receive another three to six cycles depending on response to chemotherapy. 

Consolidation chemotherapy is the addition of cycles of the taxane/platinum regimen or the addition of singleagent platinum or a single taxane after completion of first-line chemotherapy.45 If the tumor has a partial response to first-line chemotherapy evident by a significant decline in CA-125 by more than 50% of the preoperative level and/or... 

Overall survival is affected by the success of the initial surgery to debulk the tumor to less than 1 cm of disease and response to first-line chemotherapy. The CA-125 level should be monitored with each cycle, and at least a 50% reduction in CA-125 after four cycles of taxane/platinum chemotherapy is related to an improved prognosis. Patients who achieve a complete response should have follow-up examinations every 3 months, including CA-125 determination, physical examination, pelvic examination, and appropriate diagnostic scans (e.g., CT scan, MRI, or PET scan) and should be evaluated for the detection of disease. Evaluate patients for resolution of any residual chemotherapy-related side effects, including neuropathies, nephrotoxicity, ototoxicity, myelosuppression, and nausea/vomiting. 

Monitor the patient for signs of hypersensitivity reactions to taxane or platinum chemotherapy regimens. 

Primary chemotherapy with either an anthracycline- or taxane-containing regimen is recommended. The use of trastuzumab with chemotherapy is appropriate for patients with HER2-positive tumors. 

Trastuzumab, a monoclonal antibody that binds to HER2, produces response rates of 15% to 20% when used as a single agent and increases response rates, time to progression, and OS when combined with chemotherapy. It has been studied in doublet (taxane-trastuzumab vinorelbine-trastuzumab) and triplet (trastuzumab-taxane-platinum) combinations but the optimum regimen is unknown. 

Recurrent SCLC is usually less sensitive to chemotherapy. If recurrence is more than 6 months after induction chemotherapy, the original regimen can be repeated. If recurrence occurs in less than 6 months but >3 months, treatment options include a taxane, gemcitabine, topotecan, irinotecan, CAV (cyclophosphamide, doxorubicin, and vincristine), and vinorelbine. 

Both omeprazole, a proton pump inhibitor and paclitaxel, a taxane cytotoxic may cause nausea and vomiting as side-effects. Prednisolone, as with other corticosteroids, does not cause nausea and vomiting. Corticosteroids such as dexamethasone are administered to relieve nausea and vomiting, particularly that associated with chemotherapy. 

Paclitaxel is a taxane that was originally derived from the bark of the yew tree. Paclitaxel is used in cytotoxic chemotherapy for malignant disease. 

Campone M, Cortes-Funes H, Vorobiof D, et al, Vinflunine A new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy, Br J Cancer 95 1161-1166, 2006. 

In an excellent review of the literature on the interaction between radiation and the taxanes, especially looking at the effects of paclitaxel, Milas et al.(38) outline how they came to realize that reoxygenation played such a substantial role in the potentiation of tumor radioresponse. It has been well established for years that tumors contain areas of hypoxic cells that are normally 2.5 to 3 times less sensitive to radiation than normal cells (37). Both radiation and chemotherapies can cause reoxygenation through their preferential killing of those oxygenated cells that are located close to blood vessels. Milas et al. summarized observations that showed ... 

The lack of data reinforces the need to conduct randomized trials in the area of carcinoma of the bladder, and given the radiosensitizing action of the taxanes, they are worthy of consideration in these protocols. The RTOG phase I/II trial looking at concurrent cisplatin, paclitaxel, and hyperfractionated radiation with selective bladder preservation and adjuvant chemotherapy is ongoing and it may serve as the basis for future randomized trials in the area (98). 

Concurrent therapy for the treatment of more than three brain metastases using paclitaxel and radiation has been explored in a phase III trial (144). The hypothesis here being that high-dose paclitaxel in combination with cranial radiation should improve local control while providing systemically active amounts of chemotherapy. Unfortunately, there was no statically significant improvement in survival seen. There is certainly a place to further explore the benefits and toxicides experienced with concurrent taxane-based therapy with radiation in metastatic disease. The role of the taxanes in concurrent chemoradiotherapy with sarcomas and pediatric tumors has not been explored at this time. 

The initial experience with the taxanes and especially with paclitaxel in the realm of combined modality therapy has had a substantial impact on the treatment of cancers both in the United States and worldwide. Paclitaxel delivered in concert with radiation provides a classical model of the development of clinically applicable treatment strategies from laboratory-based studies. The initial in vitro works of Tishler (39) and Choy (40) have translated in a very tangible way into approaches that are clinically applicable and in the next generation of randomized clinical trials their efficacy will be compared to more traditional chemotherapies in the combined modality setting. While the experience to date with both paclitaxel and docetaxel has been largely positive, the mortality rates in many of the solid tumor types remind us that much more needs to be done. 

Rowinsky EK. The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents.AnnuRev Med 1997 48 353-374. 

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