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Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported a 62% response rate and 54% 1-year survival rate for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 24-hour infusion in combination with fixed-dose carboplatin to treat patients with advanced non-small cell lung cancer (NSCLC). Myelosuppression proved dose limiting, but was substantially reduced by the routine use of granulocyte colony-stimulating factor during the second and subsequent cycles. Activity for paclitaxel 135 mg/m2 and 200 mg/m2 by 1-hour infusion every 3 weeks in patients with NSCLC, with minimal myelosuppression and the suggestion of a dose-response relationship, has been reported. In November 1994, we initiated a phase II trial in patients with advanced, measurable, chemotherapy-naive NSCLC using paclitaxel 175 mg/m2 given in 1 hour, and carboplatin dosed to a fixed target area under the concentration-time curve of 7.5 every 3 weeks. In the absence of grade 4 myelosuppression, paclitaxel was escalated on an intrapatient basis by 35 mg/m2 per cycle to a maximum dose of 280 mg/m2 by cycle 4. Granulocyte colony-stimulating factor was not routinely used. Of the 57 patients accrued, 44 (81%) are Eastern Cooperative Oncology Group performance status 1. The median patient age is 64 years. To date, 54 patients are fully evaluable for toxicity. In the first 20 evaluable patients accrued (cohort A), myelosuppression was tolerable, but cumulative peripheral sensory neuropathy proved dose limiting: grade > or = 1 in 15 (75%) patients and grade 3 in six (30%), generally occurring at paclitaxel doses > or = 215 mg/m2 and obligating at least three patients to be removed from study despite absence of disease progression. The protocol was consequently revised. The starting dose of paclitaxel was reduced to 135 mg/m2 with intrapatient dose escalations of 40 mg/m2 per cycle, to a maximum paclitaxel dose of 215 mg/m2, recapitulating the original dosing schema used in Fox Chase Cancer Center study 93-024. For the 35 patients enrolled in the second cohort (cohort B), treatment has been better tolerated. Of 21 evaluable patients, 13 (62%) have experienced peripheral sensory neuropathy, grade 3 in only one (5%) patient. Myelosuppression also has been less pronounced, with 44% grade 4 granulocytopenia and 38% grade > or =3 thrombocytopenia in cohort B compared with 70% and 50%, respectively, in cohort A. Of the first 22 patients accrued to cohort A, 12 (55%) had major objective responses. Median event-free survival is 24 weeks and median survival is 47 weeks. Of the 35 evaluable patients in cohort B, nine (26%) have had major objective responses. Median event-free survival is 22 weeks. It is too early to report median survival. Paclitaxel given by 1-hour infusion in combination with carboplatin at a fixed target area under the concentration-time curve of 7.5, although active in advanced NSCLC, is associated with problems that compromise its efficacy. Higher dose levels yield intolerable toxicity, evidenced by the incidence of neurotoxicity (rather than myelosuppression) that was dose and protocol limiting at paclitaxel doses exceeding 215 mg/m2. Lower doses, while more tolerable, appear to be associated with lower response rates.
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PMID:Paclitaxel (1-hour) and carboplatin (area under the concentration-time curve 7.5) in advanced non-small cell lung cancer: a phase II study of the Fox Chase Cancer Center and its network. 933 Nov 28

Evidence suggests that locally advanced non-small cell lung cancer may be more effectively treated with induction chemotherapy followed by radiation or concurrent chemoradiation compared with radiation alone. The majority of combined modality regimens evaluated in mature clinical trials incorporated cisplatin-based combinations, but none has incorporated newer active systemic agents or fully examined the potential role of induction chemotherapy followed by concurrent chemoradiation. The Fox Chase Cancer Center and its affiliate network have evaluated induction chemotherapy with paclitaxel plus carboplatin with or without granulocyte colony-stimulating factor priming followed by concurrent systemic chemotherapy and radiation therapy in patients with locally advanced non-small cell lung cancer. The regimen has been well-tolerated and paclitaxel dose escalation continues. The major response to combined therapy was 55% in the first 38 evaluable patients, and the 1-year survival rate is 72%. Median survival is 15 months. The primary toxicity following induction therapy has been myelotoxicity, which has been mild in severity. During concurrent therapy, the major toxicity has been esophagitis; only limited nonhematologic toxicity has been observed. Other studies evaluating different chemoradiation regimens have reported varying results. Paclitaxel/carboplatin-based combinations, administered cyclically at or near full systemic dose in combination with radiation, are feasible. Randomized studies are needed to determine the proper sequencing, potential survival benefits, and relative safety profiles of these combined modality regimens.
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PMID:Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer. 1021 May 49

The paclitaxel/carboplatin combination has demonstrated promising activity in metastatic non-small-cell lung cancer (NSCLC); therefore, we mounted an exploratory study of these agents with thoracic radiation (TRT) in locally advanced NSCLC. Eligibility stipulated a Karnofsky performance status >or= 70%, weight loss <or= 5%, and primarily stage IIIB or bulky IIIA NSCLC. Induction chemotherapy (CT), 2 cycles of paclitaxel 175-225 mg/m2 over 3 hours and carboplatin (targeted area under the curve [AUC] of 7.5), was administered on days 1 and 22. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg was given on days 2-15 and 23-36 to all patients; half were randomized to priming G-CSF every day x 5 prior to day 1 of induction therapy. On day 43, TRT (60-63 Gy/30-34 fx) was initiated. At dose level 1, only Fox Chase Cancer Center patients received carboplatin (initial target AUC 3.75) and paclitaxel (67.5 mg/m2 over 3 hours) days 43 and 64. In the absence of dose-limiting toxicity, phase I dose escalation in 3-patient cohorts was scheduled to proceed to a maximum carboplatin AUC 7.5 and paclitaxel dose of 210 mg/m2. To date, 53 patients have received induction therapy; 4 are too early to evaluate. The portion of the study evaluating G-CSF priming revealed no myeloprotective effect, likely due to a lack of myelosuppressive toxicity with the conventionally dosed cohort. Twenty-two patients have received concurrent TRT/CT. In sequential cohorts, the chemotherapy doses on days 43 and 64 have been escalated (to paclitaxel 175 mg/m2 and carboplatin AUC 5) with 1 episode each of grade 4 granulocytopenia and grade 3 anemia. The occurrence of grade >or= 2 esophagitis has corresponded to length (> 16 cm) of esophagus in the radiation treatment field (Fisher's exact test, P = 0.006). The partial response rate to induction therapy was 40% and to the combined modality therapy was 60%. The median survival for all 49 patients is 15.3 months, with a median disease-free survival (DFS) of 7.8 months. In the subset of 22 patients treated on the phase I portion of the study, the median survival and DFS were 18.5 months and 13.5 months, respectively. Induction therapy with paclitaxel and carboplatin followed by concurrent chemoradiotherapy with the same agents is an active and well-tolerated treatment approach in locally advanced NSCLC. To date, paclitaxel 175 mg/m2 plus carboplatin AUC 5 administered at 3-week intervals for 2 cycles is safe in combination with TRT.
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PMID:Induction and concurrent paclitaxel/carboplatin every 3 weeks with thoracic radiotherapy in locally advanced non-small-cell lung cancer: an interim report. 1465 27