Seminars in oncology
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Seminars in oncology · Feb 1996
Activity and safety of epirubicin plus paclitaxel in advanced breast cancer.
We performed a dose-escalation study to evaluate the maximum tolerated dose (MTD) of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus a fixed dose of epirubicin. Epirubicin was administered as a 90 mg/m2 bolus immediately followed by a 3-hour infusion of paclitaxel starting at 135 mg/m2 and escalating by 20mg/m2 for each triplet of patients as long as no dose-limiting toxicity had occurred; courses were repeated every 3 weeks. The MTD was defined as that at which any of the following toxicities occurred in at least two of six patients: absolute neutrophil count less than 500/microliter for more that 7 days or less than 100/microliter for more than 3 days; any episode of febrile neutropenia requiring intravenous antibiotics and hospitalization; grade 4 thrombocytopenia requiring platelet transfusion; failure to recover absolute neutrophil count to > or = 1,500/microliter and/or platelets to > or = 100,000/microliter by day 28; and any grade > or = 3 nonhematologic toxicity. ⋯ In conclusion, neutropenia is the most frequent toxicity of this novel combination. However, the MTD has not yet been reached. The combination of epirubicin plus paclitaxel is highly active, and no signs of cumulative myocardiopathy have been observed.
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Seminars in oncology · Feb 1996
Paclitaxel-containing combination chemotherapy for metastatic breast cancer.
After demonstration of the marked antitumor activity against metastatic breast cancer of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), other clinical trials explored the possibility of combining this new active agent with other cytotoxic drugs with proven efficacy against breast carcinoma. Paclitaxel plus doxorubicin, thought to be the most effective single agents against breast cancer, yielded remission rates ranging from 60% to 80%, including some complete remissions. Schedule-dependent toxic interactions were observed when paclitaxel preceded the administration of doxorubicin. ⋯ Of interest are recent reports on paclitaxel and vinorelbine, showing this combination to be clearly active, with good tolerability and rapid recovery after myelosuppression. Trials of this combination are ongoing with granulocyte colony-stimulating factor support, on an every-14-day schedule. The doxorubicin/paclitaxel doublet remains the most promising in terms of activity, although other combinations with a high degree of activity and good tolerance are being sought.
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Seminars in oncology · Dec 1995
Multicenter Study Clinical TrialSingle-agent paclitaxel by 3-hour infusion in the treatment of non-small cell lung cancer: links between p53 and K-ras gene status and chemosensitivity.
Currently available cytotoxic drugs are only moderately active in non-small cell lung cancer (NSCLC) and prolong survival only slightly. In two published trials, single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was reported to have significant activity in NSCLC, with response rates of 21% and 24%. Treatment-limiting hypersensitivity reactions, however, were noted in a phase I trial of paclitaxel given as a 3-hour infusion at doses > or = 190 mg/m2. ⋯ Granulocytopenia was generally mild. Therapy was interrupted in only two patients because of the development of grade 3 neuropathy. In our experience, paclitaxel is one of the most active cytotoxic drugs targeting NSCLC.
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Seminars in oncology · Dec 1995
Meta Analysis Clinical TrialDocetaxel (Taxotere) in combination: a step forward.
Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) is a hemisynthetic derivative from European yew that inhibits tubulin depolymerization and enhances the formation of microtubule bundle aggregates, causing cell death. Activity against a variety of tumor types has been reported. Single-agent chemotherapy is rarely curative; hence, combination regimens are the logical next step in the attempt to improve tumor reduction and prolong survival. ⋯ The docetaxel/vinorelbine combination produced responses at all dose levels as front-line therapy for metastatic breast cancer; dose-limiting toxicity was experienced by two patients, but only when the vinorelbine dose was raised to 22.5 mg/m2. In phase II studies in non-small cell lung cancer, preliminary results have shown the docetaxel/cisplatin combination to have a promising level of activity and an acceptable toxicity profile. Future trials will continue to evaluate the role of docetaxel in combination and in sequential regimens, most particularly in metastatic breast cancer and non-small cell lung cancer.
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Seminars in oncology · Dec 1995
Review Clinical TrialCombined-modality therapy for advanced non-small cell lung cancer: paclitaxel and thoracic irradiation.
Despite advances in the modalities used to treat non-small cell lung cancer (NSCLC), the frequency of locoregional and distant relapses necessitates further enhancement of the therapeutic program. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated clinical efficacy against NSCLC and in vitro studies support its role as a radiation potentiator at concentrations achievable in vivo. Thus, a phase I study of weekly paclitaxel and daily concurrent thoracic radiation was conducted in patients with advanced NSCLC to determine (1) the maximum tolerated dose of paclitaxel administered on an outpatient basis for 6 consecutive weeks with daily radiation and (2) the toxicities of the paclitaxel/radiation combination. ⋯ The schedule of weekly paclitaxel and daily thoracic radiation appears active in NSCLC and can be delivered safely in the outpatient setting. The principal dose-limiting toxicity is esophagitis, and the maximum tolerated dose of paclitaxel for this schedule is 60 mg/m2/wk. A phase II trial of weekly paclitaxel 60 mg/m2 and radiation has been initiated in patients with NSCLC.