Correlation of HER2, FCGR2A, and FCGR3A gene polymorphisms with trastuzumab related cardiac toxicity and efficacy in a subgroup of patients from UNICANCER-PACS 04 trial.

The purpose of this study was to investigate, in the context of a prospective node-positive-breast cancer trial HER2 containing-regimen (UNICANCER-PACS 04 trial), the predictive value of HER2, FCGRIIA, and FCGRIIIA gene polymorphisms for cardiac toxicity and efficacy of trastuzumab. We analyzed HER2-I655V, FCGR2A-H131R, and FCGR3A-V158F single nucleotide polymorphisms in patients in adjuvant setting treated by six courses of either fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2), or epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2) every 3 weeks then randomly assigned, in case of HER2 overexpressing tumor, to either trastuzumab for 1 year or nothing. Left ventricular ejection fraction and clinical examination were monitored in each patient, seven times throughout the study to detect congestive heart failure or asymptomatic subclinical cardiac toxicity.

Phase I study of pegylated liposomal doxorubicin in combination with ifosfamide in pretreated ovarian cancer patients.

Objectives: To determine the dose limiting toxicity, the maximum tolerated dose and the recommended dose of pegylated liposomal doxorubicin (PLD) in association with a fixed dose of ifosfamide (IFO) to patients with recurrent, advanced ovarian cancer (AOC).

Methods: Patients with progressing platinum-sensitive or resistant disease were included in 5 dose levels consisting of PLD (25 mg/m2 to 45 mg/m2, day 1) combined with a fixed IFO dose administered as a continuous infusion (1700 mg/m2/d, day 1 to 3) to define the MTD on the basis of acute toxicity during the first 2 cycles, then confirm the MTD, by the evaluation of delayed toxicity (hand-foot syndrome).

Results: Forty-eight patients were treated.

Phase I-II study of pegylated liposomal doxorubicin combined with weekly paclitaxel as first-line treatment in patients with metastatic breast cancer.

Objectives: Pegylated liposomal doxorubicin (PLD) appears to be as active as doxorubicin in first-line metastatic breast cancer (MBC) patients, with lower cardiac toxicity. This phase I-II trial aimed to determine the dose limiting toxicity (DLT) and recommended dose (RD) of a first-line combination of PLD and weekly paclitaxel.

Methods: MBC patients received PLD on day 1, administered over 60 minutes IV.

A phase I and pharmacokinetic study of irofulven and cisplatin administered in a 30-min infusion every two weeks to patients with advanced solid tumors.

Background: To determine maximum tolerated dose (MTD), recommended dose, safety and pharmacokinetics of irofulven combined with cisplatin in advanced solid tumor patients.

Patients And Methods: Cisplatin and irofulven were given sequentially i.v.

Phase I and pharmacokinetic study of aplidine, a new marine cyclodepsipeptide in patients with advanced malignancies.

Purpose: To establish the safety, pharmacokinetic parameters, maximum-tolerated dose, and recommended dose of aplidine, a novel marine cyclodepsipeptide, in patients with advanced cancer.

Patients And Methods: Using a modified Fibonacci method, we performed a phase I and pharmacokinetic study of aplidine administered as a 24-hour intravenous infusion every 2 weeks.

Results: Sixty-seven patients received aplidine at a dose ranging from 0.

Phase I study with dose escalation of gemcitabine and cisplatin in combination with ifosfamide (GIP) in patients with non-small-cell lung carcinoma.

Gemcitabine (G) and cisplatin (P) are active reference agents in patients with non-small-cell lung cancer (NSCLC). Ifosfamide (I) has also been approved for NSCLC treatment. This phase I trial aimed to determine the dose-limiting toxicity (DLT), maximum tolerated dose [maximum tolerated dosage (MTD)], and recommended dose (RD) of a GIP combination in patients with advanced/metastatic NSCLC.