Seminars in oncology
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Seminars in oncology · Oct 1998
ReviewEfficacy and toxicity of irinotecan in patients with colorectal cancer.
In six published phase II trials, irinotecan (CPT-II; Camptosar; Pharmacia & Upjohn Co, Kalamazoo, MI) has demonstrated consistent activity with response rates of approximately 13% to 27% in patients with advanced colorectal cancer (CRC) refractory to 5-fluorouracil (5-FU) therapy. Similar response and median survival rates have been achieved using either the US regimen (once a week for 4 weeks followed by a 2-week rest) or the European regimen (once-every-3-week schedule). The optimal administration schedule for irinotecan is uncertain. ⋯ Irinotecan has been explored as a single agent in patients with newly diagnosed CRC and has generated response rates in the range of 19% to 32% and a median survival time of approximately 12 months, suggesting a level of antitumor activity similar to that observed with 5-FU and leucovorin. Two recently completed phase III studies in 5-FU-refractory patients have shown that treatment with irinotecan confers a survival advantage compared with treatment with infusional 5-FU or best supportive care. Current studies focus on the activity of irinotecan as part of combined chemotherapy in patients with newly diagnosed advanced-stage CRC, as part of combined-modality therapy with radiation therapy, and as adjuvant chemotherapy for patients with locally advanced CRC.
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There has been a gradual evolution in the philosophy of treatment for metastatic breast cancer. It has long been known that endocrine therapy, radiotherapy, and chemotherapy could offer substantial palliative benefits to patients with symptomatic metastases. While these quality of life issues remain crucially important, it is increasingly recognized that the survival of patients with this condition also appears to be improving as a result of therapeutic advances. ⋯ The results of phase II studies suggest that of these agents, used at the recommended doses, docetaxel (Taxotere, Rhône-Poulenc Rorer, Antony, France) may be the most active, achieving an objective response rate of 59% in minimally pretreated patients and 47% when used in second-line treatment. In these studies, docetaxel was given at the standard dose of 100 mg/m2 over 1 hour. Recent results from phase III studies in which individual studies with docetaxel and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have been compared with standard therapies indicate that docetaxel is the most active single agent in metastatic breast cancer.
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Seminars in oncology · Oct 1998
ReviewPrevention and treatment of oral mucositis following cancer chemotherapy.
The administration of many chemotherapy regimens may be complicated by toxicities that limit clinicians' abilities to deliver the most effective doses of active agents. Oral mucositis remains the dose-limiting toxicity of a variety of chemotherapeutic regimens and may result in significant morbidity, impaired nutrition, treatment delays, and dose reductions. In this report, the mechanisms of both direct and indirect stomatotoxicity are reviewed and efforts are made to help identify patient-related and treatment-related factors that predispose patients to oral mucositis. Last, various approaches to prevent and treat chemotherapy-induced mucositis are reviewed.
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Seminars in oncology · Oct 1998
Clinical TrialTaxane-based three-drug combination in metastatic and adjuvant treatment of breast cancer.
Considering the recommended dose of the docetaxel/doxorubicin combination (75 mg/m2 and 50 mg/m2, respectively), we decided to proceed with a pilot program in untreated metastatic breast cancer aimed at defining a multidrug regimen that could be later randomly compared with a standard doxorubicin-containing polychemotherapy regimen with equidoses of doxorubicin such as the FAC protocol (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) in first-line metastatic and adjuvant treatment of breast cancer patients. We proceeded with a pilot phase II study of the TAC combination, which consists of docetaxel 75 mg/m2 as a 1-hour infusion preceded by doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2, both given as an intravenous bolus. Three hundred seventy courses were delivered in 54 anthracycline-naive patients, among whom 62% had visceral metastases. ⋯ The major response rate was 73% overall and 79% in measurable disease. Time to progression and survival are still under evaluation. The TAC combination is an active and well-tolerated regimen that is the basis of two currently open, pivotal, randomized phase III trials comparing TAC with FAC in the metastatic and adjuvant treatment of breast cancer.
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Seminars in oncology · Oct 1998
Clinical TrialTaxanes in combination with doxorubicin in the treatment of metastatic breast cancer.
Given their high level of activity when used as single agents in metastatic breast cancer, the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) with doxorubicin is a logical development in the search for regimens that will improve prognosis in this disease. In a phase I trial conducted at the Institut Curie and Hospital Paul-Brousse (Paris, France), 42 women with previously untreated metastatic breast cancer received a total of 286 cycles of the combination at six dose levels. Prophylactic steroids and H1 and H2 blockers were given. ⋯ For patients receiving one of the four highest dose levels, the overall response rate was 81% (95% confidence intervals, 63% to 93%); comparable levels of response were seen at all disease sites. The doses recommended for phase II/III studies of this active and well-tolerated combination are either 50 mg/m2 doxorubicin plus 75 mg/m2 docetaxel or 60 mg/m2 of both drugs. Encouraging response rates also have been seen in studies in which paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was combined with doxorubicin, although cardiotoxicity was a significant factor in some studies.