Biomedical subjects

Michael J Boyer

Publications and source records attributed to Michael J Boyer.

3 recordsLinked to original sources

PubMed2005

A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer.

PURPOSE: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. EXPERIMENTAL DESIGN: Phase I pts received pemetrexed (day 1, 300-700 mg/m2) and vinorelbine (days 1 and 8, 15-30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given. RESULTS: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). CONCLUSION: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.

Adult↗

PubMed2004

Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer.

PURPOSE: Positron emission tomography (PET) is a costly new technology with potential to improve preoperative evaluation for patients with non-small-cell lung cancer (NSCLC). There is increasing pressure for PET to be included in standard diagnostic work-up before decisions about surgical management of NSCLC. The resource implications of its widespread use in staging NSCLC are significant. METHODS: A randomized controlled trial was conducted to investigate the impact of PET on clinical management and surgical outcomes for patients with stage I-II NSCLC. The primary hypothesis was that PET would reduce the proportion of patients with stage I-II NSCLC who underwent thoracotomy by at least 10% through identification of patients with inoperable disease. RESULTS: One hundred eighty-four patients with stage I-II NSCLC were recruited and randomly assigned; 92% had stage I disease. Following exclusion of one ineligible patient, 92 patients were assigned to no PET and 91 to PET. Compared with conventional staging, PET upstaged 22 patients, confirmed staging in 61 and staged two patients as benign. Stage IV disease was rarely detected (two patients). PET led to further investigation or a change in clinical management in 13% of patients and provided information that could have affected management in a further 13% of patients. There was no significant difference between the trial arms in the number of thoracotomies avoided (P =.2). CONCLUSION: For patients who are carefully and appropriately staged as having stage I-II disease, PET provides potential for more appropriate stage-specific therapy but may not lead to a significant reduction in the number of thoracotomies avoided.

Adult↗

PubMed2002

Pemetrexed: single-agent and combination phase I study overview.

Pemetrexed is a novel folic acid antimetabolite that exerts its activity by the inhibition of multiple enzyme targets. It has been evaluated in a series of phase I clinical trials that explored different administration schedules. The schedule that has been carried forward into phase II trials involves the administration of pemetrexed as a 10-minute intravenous infusion every 21 days with no standard pretreatment with folic acid or vitamin B(12). When given in this manner, the dose-limiting toxicities were neutropenia and thrombocytopenia. Other toxicities included mucositis, rash, and fatigue. The recommended phase II dose was 600 mg/m(2) administered intravenous every 21 days, although this was subsequently modified to 500 mg/m(2) when several early patients experienced toxicities requiring dose reduction in phase II studies. On the basis of preclinical studies suggesting additive or synergistic effects, pemetrexed has also been evaluated in phase I studies in combination with several other agents including cisplatin, carboplatin, oxaliplatin, irinotecan, the taxanes, and anthracyclines. Encouraging anticancer activity has been observed in many of these studies.

Antimetabolites, Antineoplastic↗