Seminars in oncology
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Seminars in oncology · Aug 1997
Clinical TrialIfosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer: update and preliminary survival analysis.
The primary objective of this study was to define the maximum tolerated dose and toxicity profile of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), given as a 24-hour infusion, in conjunction with ifosfamide/carboplatin/etoposide (ICE) chemotherapy in patients with advanced lung cancer. Paclitaxel was escalated from 75 to 225 mg/m2 in 25-mg/m2 increments. All patients received granulocyte colony-stimulating factor 5 microg/kg/d from day 4 until the neutrophil count was > or = 10,000/microL. ⋯ Survival was almost identical between stage IIIA and stage IV subsets. We conclude that it is possible to safely administer full-dose single-agent paclitaxel with granulocyte colony-stimulating factor support in conjunction with full-dose ifosfamide/carboplatin/etoposide chemotherapy. While response rates observed were not particularly notable, median survival is considerably longer than that usually achieved with combination chemotherapy in advanced lung cancer.
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Seminars in oncology · Aug 1997
Clinical TrialPostoperative bronchopulmonary complications in stage III lung cancer patients treated with preoperative paclitaxel-containing chemotherapy and concurrent radiation.
We previously observed encouraging results and acceptable toxicity in phase II trials testing preoperative split-course thoracic radiation and simultaneous cisplatin, etoposide, and 5-fluorouracil in stage III non-small cell lung cancer patients. We decided to delete 5-fluorouracil and to incorporate paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into our combined-modality treatment. The first group of patients received carboplatin dosed at an area under the concentration-time curve of 4 on day 2, etoposide 50 mg orally days 1 to 5 and 8 to 12, cisplatin 50 mg/m2 on day 21, and paclitaxel 35 mg/m2 escalated to 45 mg/m2 on days 1 and 8. ⋯ Postoperative complications included bronchopleural fistula in one patient each in groups 1 and 3, hypoxia in one patient in group 1, pulmonary hypertension in one patient in group 2, pneumonia in one patient in group 2, and adult respiratory distress syndrome in one patient in group 3, which proved lethal. Thus, six of 16 patients had serious postoperative complications. The relatively high incidence of postoperative bronchopulmonary complications suggests that the use of preoperative paclitaxel-containing chemotherapy and simultaneous thoracic radiation may not be feasible.
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Seminars in oncology · Aug 1997
Clinical TrialWeekly paclitaxel/cisplatin with concurrent radiotherapy in patients with locally advanced non-small cell lung cancer: a phase I study.
We designed a phase I study to determine the maximum tolerated doses of weekly cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (doses escalated alternately) when given concurrently with standard or hyperfractionated radiotherapy (RT) and to define the nature of the dose-limiting toxicity. Chemotherapy-naive patients with locally advanced non-small cell lung cancer received weekly combination cisplatin/paclitaxel with concurrent local RT. Radiation therapy was initially given at the dose of 1.2 Gy twice daily x 5 d/wk x 5 weeks (total dose, 60 Gy). ⋯ We thus conclude that the cisplatin/paclitaxel combination given weekly can be safely administered concurrent with both standard or hyperfractionated RT. Hyperfractionation is associated with a higher incidence of severe esophagitis and required a slight reduction in cisplatin dose. To verify whether the use of a daily schedule translates into a better therapeutic index, a new phase I study is under way, testing twice-daily cisplatin/paclitaxel concurrently with hyperfractionated RT.
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Seminars in oncology · Aug 1997
Clinical TrialInduction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.
Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. ⋯ No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.
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Seminars in oncology · Aug 1997
Docetaxel (Taxotere) and vinorelbine in the treatment of non-small cell lung cancer.
The efficacy and safety of a combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and vinorelbine were evaluated in two phase II studies including 46 and 39 chemotherapy-naive patients with non-small cell lung cancer, respectively. In the first study, vinorelbine 25 mg/m2 was given on day 1 and docetaxel 100 mg/m2 on day 2, with recombinant human granulocyte colony-stimulating factor support from day 5 until day 12, every 3 weeks. In the second study, docetaxel 75 mg/m2 was given on day 1 and vinorelbine 20 to 25 mg/m2 on days 1 and 5 in a 3-week schedule. ⋯ The overall response rates were 33% and 39%, respectively. It is concluded that combination therapy with docetaxel/ vinorelbine or with docetaxel/vinorelbine/cisplatin has antitumor activity in the treatment of non-small cell lung cancer. Granulocytopenia and febrile neutropenia are the most severe toxicities that limit the usefulness of these regimens.