BACKGROUND: The objective of this phase I study was to determine the maximal tolerated dose (MTD) of the combination of weekly docetaxel and exisulind in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with advanced or refractory solid tumors were treated with intravenous weekly docetaxel with daily oral exisulind. The following dose levels (docetaxel/exisulind) were explored: 30-mg/m2/200 mg po bid, 35/200, 35/250 and 40/250. Docetaxel was administered weekly for 6 weeks followed by 2 weeks off, and exisulind was taken twice daily. Each cycle was 8 weeks. RESULTS: Eighteen patients were enrolled in the study. All of them had received prior systemic therapy. Most patients had either melanoma or carcinomas of the upper gastrointestinal tract. A total of 31 cycles of therapy were administered. DLTs were grade 3 diarrhea, anorexia and fatigue and grade 3 cutaneous toxicity at dose level 4 (40/250). Myelosuppression was mild. Fatigue and gastrointestinal toxicity (anorexia, dyspepsia, nausea, abdominal pain and diarrhea) represented the most common toxicities. However, grade 3 and grade 4 toxicities were uncommon. There were no treatment related deaths. No objective responses were observed and five patients achieved stable disease. CONCLUSIONS: The recommended dose for phase II studies is weekly docetaxel 35 mg/m2 for 6 weeks followed by 2 weeks off in combination with oral exisulind 250 mg po bid. This combination is feasible and well-tolerated at these doses.
BACKGROUND: The objective of this phase I study was to determine the maximal tolerated dose (MTD) of the combination of weekly docetaxel and exisulind in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with advanced or refractory solid tumors were treated with intravenous weekly docetaxel with daily oral exisulind. The following dose levels (docetaxel/exisulind) were explored: 30-mg/m2/200 mg po bid, 35/200, 35/250 and 40/250. Docetaxel was administered weekly for 6 weeks followed by 2 weeks off, and exisulind was taken twice daily. Each cycle was 8 weeks. RESULTS: Eighteen patients were enrolled in the study. All of them had received prior systemic therapy. Most patients had either melanoma or carcinomas of the upper gastrointestinal tract. A total of 31 cycles of therapy were administered. DLTs were grade 3 diarrhea, anorexia and fatigue and grade 3 cutaneous toxicity at dose level 4 (40/250). Myelosuppression was mild. Fatigue and gastrointestinal toxicity (anorexia, dyspepsia, nausea, abdominal pain and diarrhea) represented the most common toxicities. However, grade 3 and grade 4 toxicities were uncommon. There were no treatment related deaths. No objective responses were observed and five patients achieved stable disease. CONCLUSIONS: The recommended dose for phase II studies is weekly docetaxel 35 mg/m2 for 6 weeks followed by 2 weeks off in combination with oral exisulind 250 mg po bid. This combination is feasible and well-tolerated at these doses.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: C Kouroussis; S Agelaki; D Mavroudis; J Souglakos; S Kakolyris; K Kalbakis; N Vardakis; D Reppa; D Hatzidaki; G Samonis; V Georgoulias Journal: Cancer Chemother Pharmacol Date: 2000 Impact factor: 3.333
Authors: Daniel C Chan; Keith A Earle; Tom L M Zhao; Barbara Helfrich; Chan Zeng; Anna Baron; Clark M Whitehead; Gary Piazza; Rifat Pamukcu; W Joseph Thompson; Hector Alila; Peter Nelson; Paul A Bunn Journal: Clin Cancer Res Date: 2002-03 Impact factor: 12.531
Authors: V Dieras; B Chevallier; P Kerbrat; I Krakowski; H Roche; J L Misset; M A Lentz; N Azli; M Murawsky; A Riva; P Pouillart; P Fumoleau Journal: Br J Cancer Date: 1996-08 Impact factor: 7.640