Seminars in oncology
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Seminars in oncology · Aug 1995
Clinical TrialConcurrent paclitaxel/cisplatin with thoracic radiation in patients with stage IIIA/B non-small cell carcinoma of the lung.
Nine patients with stage IIIB non-small cell lung cancer were entered into a phase II trial designed to determine the feasibility of giving a combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus cisplatin concurrent with thoracic radiation. Paclitaxel was given as a 24-hour infusion (135 mg/m2) followed by cisplatin (75 mg/m2) every 4 weeks, for a total of four cycles. Thoracic radiation was given concurrently with the first two cycles of chemotherapy, for a total dose of 64.8 Gy over 6 weeks. ⋯ All patients were able to receive the full dose of radiation, although half of the patients required some modification of the chemotherapy regimen. There was one complete response and four partial responses, yielding a 56% overall response rate. This study demonstrates that it is feasible to treat patients with stage IIIB non-small cell lung cancer with paclitaxel/cisplatin plus concurrent thoracic radiation, with a degree of toxicity comparable with that associated with a degree of toxicity comparable with that associated with other concurrent combined-modality regimens for this disease.
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Seminars in oncology · Aug 1995
Clinical TrialPreliminary analysis of a phase II study of weekly paclitaxel and concurrent radiation therapy for locally advanced non-small cell lung cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an attractive agent to combine with radiation for non-small cell lung cancer. We have been conducting clinical trials of weekly paclitaxel and concurrent radiation therapy. In a phase I study in non-small cell lung cancer, we determined the maximum tolerated dose of paclitaxel to be 60 mg/m2/wk with radiation. ⋯ Twenty percent of patients had grade 4 esophagitis. Only 8% of patients had grade 3 neutropenia. Combined-modality therapy with paclitaxel and radiation is a promising treatment for locally advanced non-small cell lung cancer with a high response rate and acceptable toxicity.
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Both gemcitabine (2',2'-difluorodeoxycytidine; dFdC) and cisplatin (cis-diammine dichloroplatinum; CDDP) are active against several solid malignancies, including ovarian cancer and head and neck squamous cell carcinoma. Because of differences in mechanisms of action and toxicity profiles, combination of the two drugs has enormous clinical potential. We studied possible synergism between the drugs: in vitro using three variants of the human ovarian cancer cell line A2780, and in vivo using gemcitabine- and cisplatin-sensitive and -resistant tumors, the head and neck cancer xenografts HNX-22B and HNX-14C and the murine syngeneic colon 26-10 tumor. ⋯ Cisplatin, injected 4 hours before or after gemcitabine, was equally active as the simultaneous schedule in HNX-22B tumors, but more toxic. In conclusion, the combination of gemcitabine and cisplatin can be synergistic in vitro and at least additive in vivo; this synergism is schedule dependent. The mechanism cannot be explained by gemcitabine triphosphate accumulation or DNA damage studies.
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Seminars in oncology · Jun 1995
ReviewNew treatment agents for advanced small cell and non-small cell lung cancer.
The cure rate for lung cancer remains low (13%) primarily due to early systemic spread and the inability to cure systemic disease. These facts have led to pessimism regarding the role of chemotherapy, especially in non-small cell lung cancers. ⋯ Early combination studies show even higher response rates when paclitaxel is combined with cisplatin or carboplatin. Ultimately, randomized trials will be needed to define the optimal use of paclitaxel and other recently developed new agents in lung cancer.
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Seminars in oncology · Jun 1995
ReviewEastern Cooperative Oncology Group studies of paclitaxel and doxorubicin in advanced breast cancer.
Based on their single-agent activity in metastatic breast cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and doxorubicin have been alternated and combined in Eastern Cooperative Oncology Group studies to identify a tolerable dose and schedule. A pilot trial in patients who had received no more than one prior chemotherapy regimen alternated paclitaxel 200 mg/m2 and doxorubicin 75 mg/m2 every 3 weeks. Seven of 12 patients had objective (complete plus partial) responses. ⋯ This combination has been incorporated as a treatment arm in an ongoing randomized prospective phase III Intergroup trial. By comparing the combination with both drugs as single agents (with crossover to the opposite agent at disease progression), investigators will attempt to assess response, toxicity, and time to progression as well as the degree of cross-resistance between the two agents. Given the poor prognosis of patients with advanced breast cancer, the three arms also will be evaluated in terms of patients' quality of life.