Seminars in oncology
-
Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a camptothecin analog, is a novel and specific inhibitor of the nuclear enzyme topoisomerase I. In preclinical studies, topotecan demonstrated significant in vitro activity in a variety of solid tumor explants derived from colorectal, breast, ovarian, renal cell, non-small cell lung cancer, and gastrointestinal sources. Notable activity was also demonstrated in vivo in a wide range of animal tumor models. ⋯ Myelosuppression was the major dose-limiting toxicity across all schedules, and nonhematologic toxicities were generally mild. Data from phase I studies have provided valuable information about antitumor responses, maximum tolerated doses, and dose-limiting toxicities associated with different dosing schedules. Based on this information, there was substantial enthusiasm for further evaluating topotecan in a wide range of cancer patients in phase II studies.
-
Seminars in oncology · Dec 1997
ReviewStereotactic radiosurgery and radiotherapy: new developments and new directions.
Stereotactic irradiation is a precise method for the delivery of focused radiation beams to small intracranial targets. Treatment can be administered in single or multiple fractions (radiosurgery or stereotactic radiotherapy, respectively). The technology has evolved rapidly because of advances in both hardware and software design. Clinical indications are unfolding through the prospective trial mechanism.
-
Seminars in oncology · Oct 1997
ReviewSystemic treatment options in advanced colorectal cancer: perspectives on combination 5-fluorouracil plus leucovorin.
A variety of 5-fluorouracil (5-FU)- based chemotherapy regimens have been investigated in colorectal cancer patients in randomized trials over the past decade. The standard regimen for treatment of colorectal cancer is combination 5-FU plus leucovorin (LV). The results from 12 randomized trials indicate that 5-FU/LV is more active than single-agent 5-FU (25% v 14% of evaluable patients); however, median survival was unchanged (12.2 months v 11.4 months, respectively). ⋯ Other modulatory strategies that appear to produce higher response rates than single-agent intravenous push 5-FU include sequential methotrexate/5-FU (19% v 10%) and continuous infusion schedules (22% v 14%). Although 5-FU-modulated strategies improve response rates over those observed with single-agent 5-FU, median survival in multi-institutional trials unfortunately has not generally exceeded 12 months. The mechanism of action, clinical activity, and toxicity of single-agent 5-FU and 5-FU-modulated regimens are reviewed.
-
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.