Seminars in oncology
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Seminars in oncology · Feb 1996
ReviewRole of paclitaxel in the treatment of breast cancer: the American Cooperative Group Experience.
Phase I and II trials to evaluate paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a single agent and combined with other drugs have generated considerable enthusiasm for this interesting new agent. Despite these trials, or because of them, many important questions remain regarding the use of paclitaxel. Ongoing Cooperative Oncology Group trials investigating the use of paclitaxel in breast cancer include CLB 9342, examining the question of paclitaxel dose intensity; the National Surgical Adjuvant Breast Project trial B-26, investigating the question of duration of infusion; E1193, testing the relative activity and synergy of paclitaxel and doxorubicin in a metastatic setting; and CLB 9344, focusing on the adjuvant use of paclitaxel. The cooperative groups are currently investigating novel paclitaxel-based combination therapy in phase II trials.
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Seminars in oncology · Feb 1996
Clinical TrialPhase I study of paclitaxel and epirubicin in patients with metastatic breast cancer: a preliminary report on safety.
Attempting to develop a new active, convenient regimen, we initiated a phase I study of paclitaxel (Taxol; Bristol-Myers squibb Company, Princeton, NJ) combined with epirubicin (Farmitalia Carlo Erba, Milan, Italy) in patients with metastatic breast cancer. In addition to standard eligibility criteria, patients with chemotherapy-naive metastasis and at least one measurable lesion had to have left ventricular ejection fractions of at least 50%; the metastatic relapse had to have occurred more than 6 months after adjuvant treatment. Anthracycline-pretreated patients could not have received cumulative doses of more than 300 mg/m2 doxorubicin, 450 mg/m2 epirubicin, or 70 mg/m2 mitoxantrone. ⋯ We conclude that the combination paclitaxel/epirubicin is safe for patients with metastatic breast cancer and, at this early evaluation, shows promising antitumor activity. Additional patients will be treated at dose level 5 to confirm whether dose-limiting toxicity occurs at this step. Indeed, we took into consideration that dose-limiting toxicity observed at this particular dose level in two of three patients might be due to hazard, since paclitaxel dose escalation up to 250 mg/m2 was further possible in association with 50 mg/m2 epirubicin.
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Seminars in oncology · Feb 1996
Review Comparative StudyThe role of taxanes in the treatment of breast cancer.
The taxanes paclitaxel and docetaxel are undergoing extensive evaluation in women with breast cancer in the United States and in Europe. Their dose-limiting toxicity is neutropenia. Paclitaxel also causes peripheral neuropathy, while docetaxel can cause unpredictable and severe skin toxicity, as well as edema and effusions due to a capillary leak syndrome. ⋯ These results clearly indicate that the taxanes will become a standard component of initial chemotherapy for women with breast cancer. The definition of their actual role still requires an answer to the unresolved questions of their optimal dose and combination with other anticancer agents. Most importantly, the drugs should be prospectively evaluated in a randomized study using comparable doses and schedules to assess which of the two has the better therapeutic index in breast cancer.
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Seminars in oncology · Feb 1996
ReviewPaclitaxel and doxorubicin, a highly active combination in the treatment of metastatic breast cancer.
The activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been documented in untreated and previously treated metastatic breast cancer, including both patients with anthracycline-resistant disease and those with extensive pretreatment. Such activity has prompted investigations of the optimal doses and schedules of paclitaxel/doxorubicin combinations. With one exception, paclitaxel has been administered as either a 24- or a 3-hour infusion, while the administration times for doxorubicin vary from bolus injection to 72-hour infusion. ⋯ Cardiotoxicity also occurred, as 15 patients had a significant decrease in left ventricular ejection fraction measured by isotope cardiography. Six of these developed congestive heart failure. This effect has been observed only in studies using short infusions of both drugs, and it is now being investigated whether lowering the peak doxorubicin concentration will preclude it.
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Seminars in oncology · Feb 1996
ReviewCPT-11 in the treatment of colorectal cancer: clinical efficacy and safety profile.
CPT-11 (irinotecan) is a promising anticancer agent with a novel mechanism of action dependent on the inhibition of the DNA eukaryotic enzyme, topoisomerase I. The clinical utility of CPT-11 in advanced colorectal cancer has been documented in more than 400 patients recruited in phase II clinical trials in Europe, Japan, and United States. Among 178 eligible patients in a multicenter European study, the overall response rate to CPT-11 on a once-every-3-weeks regimen was 18%, and the median duration of response was 9.1 months. ⋯ CPT-11 appears to have activity similar to that of 5-FU in first-line treatment and, moreover, remains active after failure of 5-FU therapy. The specific gastrointestinal toxicity is manageable, and a better control of this type of toxicity is expected in the future. CPT-11 would therefore appear a welcome addition to the oncology armamentarium for this difficult-to-treat malignancy.