Seminars in oncology
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Seminars in oncology · Oct 1997
Clinical TrialA phase II study of repetitive cycles of dose-intense carboplatin plus paclitaxel chemotherapy and peripheral blood stem cells in metastatic breast cancer.
To assess the feasibility of administering sequential cycles of dose-intensive therapy, 14 patients without prior chemotherapy for metastatic breast cancer were registered to be treated with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) at an initial dose of 250 mg/m2 over 24 hours (day 1), followed by carboplatin dosed to an area under the concentration-time curve of 16 (calculated according to the Calvert formula), every 3 weeks for four cycles. This combination was supported with peripheral blood stem cells collected following granulocyte colony-stimulating factor with or without cyclophosphamide and paclitaxel. One patient failed to peripheralize CD34 cells after cyclophosphamide/paclitaxel therapy and was taken off protocol. ⋯ Of the nine patients who entered the paclitaxel/carboplatin phase and were evaluable for response, five achieved a complete remission. This doublet of high-dose therapy can be given in an entirely ambulatory setting and is associated with modest hematologic toxicity. The value of this option in the treatment of metastatic breast cancer compared with more conventional approaches to high-dose therapy will require a greater number of patients evaluable for response and longer follow-up.
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Seminars in oncology · Oct 1997
Clinical TrialInfusional 5-fluorouracil/leucovorin plus paclitaxel and cisplatin in the first-line treatment of metastatic breast cancer: results of a phase II study.
Our phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose, 24-hour infusional 5-fluorouracil (5-FU)/leucovorin (LV) in intensively pretreated patients with metastatic breast cancer prompted the addition of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to the regimen for a phase I/II study of outpatient second-line treatment of metastatic breast cancer. That study further prompted the addition of cisplatin to the regimen for first-line treatment. Twenty-eight patients with metastatic breast cancer have been evaluated. ⋯ Overall response was 82% (95% confidence interval, 66% to 100%). We conclude that the combination of paclitaxel/cisplatin with weekly high-dose infusional 5-FU/LV appears to be effective in the first-line treatment of metastatic breast cancer. Preliminary results must be confirmed by the final analysis of response duration, time to progression, and survival.
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Seminars in oncology · Oct 1997
Clinical TrialPaclitaxel plus doxorubicin in metastatic breast cancer: preliminary analysis of cardiotoxicity.
This ongoing phase II trial was designed to determine the antitumor activity and cardiotoxicity of a combination of doxorubicin (50 mg/m2) and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 to 225 mg/m2 over 3 hours) as first-line chemotherapy for metastatic breast cancer. Of 76 patients entered so far, 57 who had received at least three courses of chemotherapy are assessable for efficacy and cardiac toxicity. A slight majority (57%) of the patients entered had prior adjuvant chemotherapy, including 33% with anthracycline-containing combinations. ⋯ The remaining five patients had LVEF decreases that fell below the lower limits of normal (33% to 48%). None of the patients developed clinically evident heart failure. Our results indicate that the combination of doxorubicin (50 mg/m2) plus paclitaxel (175 to 225 mg/m2) is effective and does not induce a clinically relevant cardiotoxicity.
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Seminars in oncology · Aug 1997
ReviewDocetaxel (Taxotere) for the treatment of anthracycline-resistant breast cancer.
Until the introduction of the taxoids, docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), in the 1990s, anthracyclines were widely recognized as the best single agents for the treatment of breast cancer. However, even when anthracyclines are used in combination regimens with response rates of over 50%, including complete responses in 17% of patients, few women (3%) with metastatic disease remain disease free at 5 years after treatment. The low level of sustained responses is largely due to the phenomenon of drug resistance. ⋯ The overall response rate to docetaxel monotherapy in patients with anthracycline-resistant or refractory metastatic disease has been shown to be 41%. The response rate to first-line docetaxel monotherapy for metastatic breast cancer has been shown to be 61%, suggesting that two thirds of the activity of docetaxel is retained in anthracycline-resistant disease. Treatment with a simultaneous combination of docetaxel and doxorubicin has been found to be very active, with a response rate of 89%, and trials to exploit the lack of cross-resistance between these agents, in sequential regimens and adjuvant therapies, are under way.
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Seminars in oncology · Aug 1997
Randomized Controlled Trial Multicenter Study Clinical TrialCarboplatin plus paclitaxel as first-line chemotherapy in previously untreated advanced ovarian cancer. German AGO Study Group Ovarian Cancer. Arbeitsgemeinschaft Gynäkologische Onkologie.
Since publication of the results of the Gynecologic Oncology Group (GOG) III study, the combination of cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been adopted widely as the new standard for treating advanced ovarian cancer. Further attempts to optimize first-line chemotherapy with platinum and taxanes include substituting carboplatin for cisplatin, individualizing the carboplatin dose by calculating it according to the area under the concentration-time curve, and reducing the length of the paclitaxel infusion. Attempts to optimize platinum/paclitaxel combinations have led to the initiation of several small phase I/II trials evaluating the carboplatin/paclitaxel combination. ⋯ Retrospective comparison with the GOG results reveals no significant difference in response rates between patients in the cisplatin/paclitaxel arm of GOG III and those in the AGO study: the GOG study reported a 73% response rate, compared with a preliminary 75% response rate in the AGO study, resulting in a relative risk of 1.03 (95% confidence interval, 0.83 to 1.27). Overall, this interim analysis did not reveal any reason to terminate this study early. Accrual is ongoing and is expected to be completed in 1997.