Seminars in oncology
-
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.
-
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.
-
Seminars in oncology · Dec 1995
ReviewTaxoids: effective agents in anthracycline-resistant breast cancer.
The results of recent clinical trials have shown that docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France), like paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), has high levels of activity in patients with anthracycline-resistant breast cancer. Agents that are at least partially non-cross-resistant with anthracyclines are especially promising for the treatment of breast cancer; the taxoids (docetaxel and paclitaxel) are such agents. Although preclinical evaluations shows clear instances of strong cross-resistance (particularly in cells lines expressing the P-glycoprotein, multidrug resistance), high response rates have been reported in patients with prior anthracycline exposure and/or anthracycline resistance. ⋯ In some studies using regimens combining doxorubicin and paclitaxel, unanticipated toxicities have occurred, such as typhlitis, as well as congestive heart failure at lower than expected cumulative doses of doxorubicin. Phase II and III studies of regimens including both anthracyclines and taxoids have been initiated. Docetaxel and paclitaxel appear to be valuable agents for use in anthracycline-resistant breast cancer patients, and may find a place in anthracycline-containing combination regimens.
-
Seminars in oncology · Dec 1995
Clinical TrialA phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results.
Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. ⋯ No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.
-
Seminars in oncology · Dec 1995
Meta AnalysisDocetaxel (Taxotere): an effective agent in the management of second-line breast cancer.
Despite improvements in detection and management, metastatic breast cancer remains a leading cause of death among women in industrialized countries. Chemotherapy is the initial treatment of choice for patients with a negative estrogen receptor status, as well as for those with a positive estrogen receptor status who have failed to respond to endocrine treatment. Patients who fail on first-line chemotherapy become candidates for second-line salvage chemotherapy; the outlook for these patients is poor, and new active agents continue to be sought. ⋯ Docetaxel also was found to be highly effective in patients with a poor prognosis, having metastases in three or more organs (53%), and/or visceral sites of disease (47%). Furthermore, the overall response rate for docetaxel in the intent-to-treat population (42.5%) is superior to the response rate of either doxorubicin as second-line therapy (29.3%) or paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ) when used as first- or second-line therapy (29%) in metastatic disease. In conclusion, docetaxel appears to be a very effective therapeutic option for women with second-line metastatic breast cancer.