Seminars in oncology
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Seminars in oncology · Dec 1995
ReviewTreatment of metastatic breast cancer with paclitaxel and doxorubicin.
The activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) against untreated and previously treated metastatic breast cancer (documented in anthracycline-resistant disease and in extensively pretreated patients as well) has prompted investigations of the optimal doses and schedules of paclitaxel/doxorubicin combinations. With one exception, paclitaxel has been administered in either a 24- or a 3-hour infusion, while the administration times for doxorubicin vary from bolus injection to a 72-hour infusion. Results of these completed phase I and II trials are reviewed. ⋯ Despite grades 3 and 4 neutropenia in 31% and 60% of courses, respectively, only six patients have been hospitalized for febrile neutropenia. Of concern, the left ventricular ejection fraction has decreased to below normal in six patients and two have developed symptomatic congestive heart failure. Whether lowering the peak doxorubicin concentration will preclude this effect, which has been observed only in the studies using short infusions of both drugs, is under investigation.
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Seminars in oncology · Dec 1995
Clinical TrialPhase I/II study of paclitaxel plus cisplatin as first-line chemotherapy for advanced non-small cell lung cancer: preliminary results.
From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). ⋯ In conclusion, at these doses of paclitaxel and cisplatin, the dose-limiting neurologic toxicity is dose dependent and cumulative after a total paclitaxel dose of approximately 1,300 mg/m2. This combination is highly active, with a total objective response rate of 38% and an objective response rate of 47% at paclitaxel doses of 200 mg/m2 or higher. Further evaluation is warranted.
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Seminars in oncology · Dec 1995
Review Clinical TrialCombined-modality therapy for advanced non-small cell lung cancer: paclitaxel and thoracic irradiation.
Despite advances in the modalities used to treat non-small cell lung cancer (NSCLC), the frequency of locoregional and distant relapses necessitates further enhancement of the therapeutic program. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated clinical efficacy against NSCLC and in vitro studies support its role as a radiation potentiator at concentrations achievable in vivo. Thus, a phase I study of weekly paclitaxel and daily concurrent thoracic radiation was conducted in patients with advanced NSCLC to determine (1) the maximum tolerated dose of paclitaxel administered on an outpatient basis for 6 consecutive weeks with daily radiation and (2) the toxicities of the paclitaxel/radiation combination. ⋯ The schedule of weekly paclitaxel and daily thoracic radiation appears active in NSCLC and can be delivered safely in the outpatient setting. The principal dose-limiting toxicity is esophagitis, and the maximum tolerated dose of paclitaxel for this schedule is 60 mg/m2/wk. A phase II trial of weekly paclitaxel 60 mg/m2 and radiation has been initiated in patients with NSCLC.
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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.
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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.