Seminars in oncology
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Seminars in oncology · Oct 1995
Clinical TrialA clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulocyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer.
We have developed a regimen incorporating multiple cycles of high-dose carboplatin and fixed-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with granulocyte colony-stimulating factor and peripheral blood stem cell support given every 21 days for up to four cycles. Our phase I study of this regimen has treated 26 patients with good performance status and histologically documented unresectable or metastatic carcinoma, sarcoma, or melanoma, 21 of whom received all planned courses every 21 days. Paclitaxel 250 mg/m2 was infused over 24 hours, followed by a 1-hour carboplatin infusion, with doses escalated between area under the concentration-time curve (AUC) targets of 8 and 20. ⋯ Among 25 evaluable patients, preliminary results show one complete response (ovarian cancer) and 11 partial responses, including four in patients with non-small cell lung cancer. Additional issues to be addressed include the effect of a shorter (or longer) paclitaxel infusion on the carboplatin AUC (and the incidence of toxicity) and whether the discrepancy between actual and predicted AUCs (greater in our study than reported elsewhere) is due to the variability of creatinine clearance-determined glomerular filtration rate or to altered carboplatin pharmacokinetics when a short high-dose infusion follows paclitaxel. Additional patients are being accrued at the AUC of 18.
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Seminars in oncology · Oct 1995
Doxorubicin/paclitaxel combination chemotherapy for metastatic breast cancer: the Eastern Cooperative Oncology Group experience.
The addition of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to the therapeutic armamentarium for breast cancer has resulted in novel opportunities and challenges for the clinician. In a series of trials that began in 1992, the Eastern Cooperative Oncology Group (ECOG) investigated the role of paclitaxel in combination with doxorubicin for the treatment of patients with advanced breast cancer. The design of the first trial, a limited-institution pilot study, involved alternating doxorubicin and paclitaxel as single agents. ⋯ This trial will close to accrual in September 1995, and analysis of the trial should provide useful information regarding the potential synergy of doxorubicin and paclitaxel, the degree of cross-resistance between the two compounds, and the relationship between steady-state paclitaxel levels and response to therapy. In addition, ECOG is currently conducting a trial designed to confirm the striking activity of cisplatin and paclitaxel seen in the British Columbia trials. Future trials by the group will examine means of combining paclitaxel with other active agents.
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Seminars in oncology · Oct 1995
Review Comparative StudyCarboplatin versus cisplatin in ovarian cancer.
The predominant data from clinical trials of advanced ovarian cancer have documented that carboplatin is equivalent to cisplatin in activity and causes considerably less ototoxicity, neurotoxicity, and nephrotoxicity. A large meta-analysis of over 2,000 patients entered into phase III clinical studies showed that patients with advanced ovarian cancer had virtually identical survival durations when treated with carboplatin- versus cisplatin-containing regimens. Furthermore, in the recent National Institutes of Health Consensus Conference on Ovarian Cancer, it was concluded that "data from mature randomized clinical trials have indicated that the combination of carboplatin and cyclophosphamide is effective therapy" and that "the substitution of carboplatin for cisplatin leads to more acceptable toxicity." Cisplatin appears to be the analog of choice for intraperitoneal therapy, which has proven superior to intravenous (IV) therapy in a recently completed intergroup study. ⋯ In the SWOG, two different high-dose regimens followed by autologous bone marrow transplantation are being evaluated in the setting of a phase II randomized trial. These regimens include high-dose carboplatin/cyclophosphamide/mitoxantrone and high-dose cisplatin/cyclophosphamide/thiotepa. The results of these and other GOG and SWOG trials will dictate the management of advanced ovarian cancer through the end of the century.
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Standard treatment for patients with advanced ovarian cancer has been cytoreductive surgery followed by combination chemotherapy. Until recently, platinum-based chemotherapy was considered optimal and patients were treated with regimens built around either cisplatin or carboplatin. Recently, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been shown to be a highly active agent in refractory ovarian cancer patients. ⋯ All current Gynecologic Oncology Group protocols for untreated patients with ovarian cancer use a paclitaxel-based regimen. These clinical trials are evaluating the relative efficacy of carboplatin plus paclitaxel versus cisplatin plus paclitaxel as well as differences in dose and schedule and number of cycles of treatment. Investigational studies are continuing with high-dose chemotherapy that requires hematologic support as well as with intraperitoneal therapy (cisplatin or paclitaxel).