Seminars in oncology
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Seminars in oncology · Dec 1996
Review Randomized Controlled Trial Comparative Study Clinical TrialThe North American experience with paclitaxel combined with cisplatin or carboplatin in lung cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a new cytotoxic chemotherapeutic agent with a novel mechanism of action. Single-agent paclitaxel studies have shown promising activity in both small cell and non-small cell lung cancers. In non-small cell lung cancer, response rates of 22% to 26% and 1-year survival rates of 40% were reported with both 3-hour and 24-hour infusions of paclitaxel. ⋯ Thrombocytopenia occurred less frequently than expected. One completed randomized study showed that the paclitaxel/cisplatin regimen was superior to the etoposide/cisplatin regimen with respect to response rate and survival. Additional randomized studies are necessary to determine whether the combinations are superior to single-agent paclitaxel, to define the optimal dose with the 3-hour infusion schedule, to define the optimal schedule (3 hours v 24 hours), and to determine whether paclitaxel can be combined with other new agents.
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Seminars in oncology · Dec 1996
Randomized Controlled Trial Clinical TrialOne-hour paclitaxel in the treatment of non-small cell lung cancer.
This review describes studies with two paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)-containing treatments for non-small cell lung cancer (NSCLC). In an ongoing study, 100 patients with previously untreated stage IIIB or IV NSCLC received combination therapy comprised of paclitaxel 225 mg/m2 via 1-hour infusion and carboplatin, dosed to an area under the concentration-time curve of 6.0. Both drugs were given intravenously and cycles were repeated every 21 days. ⋯ Grade 3/4 esophagitis was observed in 51% of participants and usually occurred during the final 2 weeks of combined-modality therapy. The combination of paclitaxel and carboplatin is active and well tolerated in patients with advanced NSCLC, and paclitaxel-based combined-modality therapy produced a high rate of complete and partial responses and encouraging survival data. Continued investigation and refinement of these regimens is ongoing.
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Seminars in oncology · Dec 1996
Multicenter Study Clinical TrialCombination paclitaxel (1-hour) and carboplatin (AUC 7.5) in advanced non-small cell lung cancer: a phase II study by the Fox Chase Cancer Center Network.
We have previously reported a 62% response rate and 54% 1-year survival rate for patients with advanced non-small cell lung cancer (NSCLC) treated with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion in combination with carboplatin, using area under the concentration-time curve dosing (FCCC 93-024). Myelosuppression proved dose limiting, but was substantially reduced by the routine use of granulocyte colony-stimulating factor during the second and subsequent cycles. Antitumor activity has been reported with minimal myelosuppression, with paclitaxel 135 and 200 mg/m2 given every 3 weeks by 1-hour infusion to patients with NSCLC. ⋯ It is too early to report survival data. In conclusion, paclitaxel by 1-hour infusion in combination with carboplatin at a fixed targeted area under the concentration-time curve of 7.5 is an active regimen in advanced NSCLC. Neurotoxicity, rather than myelosuppression, is dose and protocol limiting at paclitaxel doses exceeding 215 mg/m2.
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Seminars in oncology · Dec 1996
Multicenter Study Clinical TrialPaclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer.
Previously untreated patients with stages IIIA or IIIB non-small cell lung cancer entered this phase II study to evaluate the activity and toxicity of combined paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin and concurrent radiation. Patients received paclitaxel 50 mg/m2/wk as a 1-hour infusion and carboplatin area under the concentration-time curve of 2/wk for 7 weeks with radiation to the primary tumor and regional lymph nodes (44 Gy) followed by a boost to the tumor (22 Gy). In addition, patients received two additional cycles of paclitaxel 200 mg/m2 and carboplatin (area under the concentration-time curve of 6) 3 weeks apart. ⋯ Seven of the nine patients recovered from the esophagitis within 2 weeks and received the additional two cycles of paclitaxel 200 mg/m2 and carboplatin (area under the concentration-time curve of 6). Only one patient (4%) had grade 4 pneumonitis; this patient also recovered within 2 weeks and received the final two doses of combined chemotherapy. Therapy with paclitaxel, carboplatin, and concurrent radiation is a promising treatment for patients with locally advanced non-small cell lung cancer; it has a high response rate and acceptable toxicity.
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Seminars in oncology · Dec 1996
Clinical TrialPhase I dose-escalation trial of paclitaxel and ifosfamide in patients with advanced non-small cell lung cancer.
This phase I dose-escalation study was undertaken to determine the maximum tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and ifosfamide that could be administered without growth factors to previously untreated patients with non-small cell lung cancer. Forty patients with advanced non-small cell lung cancer were treated with a 3-hour infusion of paclitaxel and a 1-hour infusion of ifosfamide, repeated every 3 weeks. Groups of three patients each entered at escalating dose levels in a traditional phase I design. ⋯ The median survival was 9.1 months (range, 1 to 12 months). In summary, outpatient paclitaxel given over 3 hours and single-dose ifosfamide given over 1 hour may be combined safely without hematopoietic growth factors for the treatment of patients with non-small cell lung cancer. The recommended doses for phase II study are paclitaxel 225 mg/m2 and ifosfamide 4 g/m2, every 3 weeks.