Seminars in oncology
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Seminars in oncology · Oct 1995
Clinical TrialFeasibility and pharmacokinetics of paclitaxel, carboplatin, and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck and for regionally advanced non-small cell lung cancer.
Sequential chemotherapy and radiotherapy offer considerable improvements in the care of patients with locally advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Improved survival for lung cancer and organ preservation in head and neck cancer have occurred with this approach, but local control remains a problem. Concurrent chemotherapy and radiotherapy can potentially improve both local control and control of micrometastases. ⋯ Plasma pharmacokinetics have shown that concurrent carboplatin and radiotherapy do not alter the pharmacokinetic behavior of paclitaxel compared with single-agent data. Concurrent therapy with carboplatin, paclitaxel, and radiotherapy is feasible on this schedule. Further case accrual to assess efficacy is ongoing.
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Seminars in oncology · Aug 1995
Clinical TrialA phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer.
A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. ⋯ The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.
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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 · Aug 1995
Randomized Controlled Trial Comparative Study Clinical TrialDose-finding and sequencing study of paclitaxel and carboplatin in non-small cell lung cancer.
A dose-finding study was set up to identify the optimal dose of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin for phase II studies in patients with advanced chemotherapy-naive non-small cell lung cancer (NSCLC). The influence of drug sequence on the toxicity and pharmacokinetics of both agents was also assessed. To develop an ambulatory regimen for palliation of advanced NSCLC, paclitaxel was infused over 3 hours with standard premedication and carboplatin over 30 minutes. ⋯ At the highest paclitaxel dose (250 mg/m2 with carboplatin 350 mg/m2) a toxic death due to severe leukopenia, thrombocytopenia, and hemorrhage occurred. Safe doses for phase II trials in untreated NSCLC are 200 mg/m2 paclitaxel with 300 mg/m2 carboplatin. Of 50 evaluable patients, five of the six major responses were observed at paclitaxel doses of 175 mg/m2 and above, which suggests a dose-response relationship for paclitaxel in NSCLC.