Escalated dose docetaxel (TXT) with G-CSF support in patients (PTS) with solid tumours

Mitchell, Patricia L.; Basser, Russel; Ng, Siew C.; Gibbs, Peter; Chipman, M; Grigg, AP; Gargano, Julia W.; Riva, A.; Appia, F.; Green, M.

doi:10.1016/s0959-8049(99)81577-9

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“…However, the answer to this question can only be answered by a prospective comparative trial. Furthermore, recent evidence would indicate that docetaxel can only be escalated modestly even when administered alone with growth factor support; Mitchell et al 30 reported that at a dose of 170 mg/m 2 DLTs of neuropathy and skin toxicity were observed associated with substantial aesthenia (personal communication). Taken together, we believe that adding taxanes to HDT regimens without compromising the alkylating agents is a promising approach requiring further investigation of efficacy, particularly in patients who have had substantial exposure to anthracyclines where they cannot be incorporated into the HDT regimen.…”

Section: Discussionmentioning

confidence: 99%

Repetitive high-dose therapy with cyclophosphamide, thiotepa and docetaxel with peripheral blood progenitor cell and filgrastim support for metastatic and locally advanced breast cancer: results of a phase I study

Prince

Rischin

Toner

et al. 2000

Bone Marrow Transplant

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Summary:This phase I study was designed to determine the optimal dosages of a novel repetitive high-dose therapy regimen for patients with metastatic breast cancer (MBC). The planned treatment was three cycles of high-dose cyclophosphamide, thiotepa and docetaxel delivered every 35 days with progressive dose-escalation in successive cohorts. Each cycle was supported by peripheral blood progenitor cells (PBPC) and filgrastim. Eighteen patients were entered into this trial. Of the planned 54 treatment cycles, 44 were delivered and 11 patients completed all three cycles. The dose-limiting toxicities were interstitial pneumonitis and mucositis with moderately severe diarrhea (n = 3) and rash (n = 3). There were no treatment-related deaths. Of the 17 patients with evaluable disease, 16 patients responded with six patients achieving a complete remission and an additional four patients achieving no detectable disease (negative restaging including PET scan) but a persistently abnormal bone scan. At a median follow-up of 12 months, median progression-free survival was 11 months with the median overall survival not reached. must still be considered investigational. 6-8 Nonetheless, one approach considered worthy of further investigation is the use of repeated cycles of HDT. 6 We have been interested in developing protocols utilizing repetitive cycles of HDT for patients with MBC, based on administering three cycles of HDT, with each cycle supported by PBPCs.9-11 The primary objective of this study was to develop a suitable regimen that could be delivered largely on an out-patient basis (ie not requiring parenteral nutrition or opiate analgesia for gastrointestinal toxicity) that could subsequently be tested in a randomized trial in patients with MBC.We have previously reported our results of repetitive cycles of HDT using a combination of ifosfamide, thiotepa and paclitaxel (ITP). 9 However, in that study, two patients developed grade 3 renal tubular acidosis (RTA) and we later recognized a further case of RTA in the subsequent phase II study of this regimen.12 Consequently, it was considered that this ifosfamide-related side-effect was unacceptable and in the current study we substituted cyclophosphamide for ifosfamide. Furthermore, as the planned randomized study was to utilize docetaxel in the conventionaldose therapy (CDT) arm, we have substituted docetaxel for paclitaxel in this high-dose therapy regimen. Materials and methods Eligibility criteriaPatients with histologically proven metastatic or locally advanced breast cancer were eligible for entry into this prospective trial. Sufficient PBPCs to support these three cycles of HDT were collected prior to the initiation of HDT (see below). Patients were ineligible if they had a history of prior docetaxel therapy, ventricular arrhythmia, myocardial infarction within 6 months of enrolment, congestive heart failure, hypersensitivity to any of the study drugs, were pregnant or lactating, had an ECOG performance status Ͼ2, life expectancy of less than 2 months, absolute ne...

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Section: Discussionmentioning

confidence: 99%