COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy.

BACKGROUND: This prospective study evaluated the relationship between arthralgia and compliance during the first year of adjuvant anastrozole therapy in postmenopausal women with hormone receptor-positive early breast cancer. PATIENTS AND METHODS: COMPliance and Arthralgia in Clinical Therapy (COMPACT) was an open-label, multicenter, noninterventional study conducted in Germany. Patients had started adjuvant anastrozole 3-6 months before the study start. The primary end points were arthralgia, compliance, and the relationship between compliance and arthralgia, assessed at specific time points. RESULTS: Overall, 1916 patients received upfront anastrozole. Mean arthralgia scores were increased from baseline at each visit up to 9 months. Compliance with anastrozole therapy gradually decreased over time from baseline to 9 months (P<0.001). At 9 months, investigators estimated that >95% of patients were compliant versus patient reports of <70%. There was a significant association between arthralgia mean scores and noncompliance at 6 months (P<0.0001), 9 months (P<0.0001), and overall (P<0.0001). Over time, new events or impairment of existing arthralgias were reported in 14% (3 months), 11% (6 months), and 9% (9 months) of patients. CONCLUSION: Arthralgia is important in the clinical management of women with early breast cancer and may contribute to noncompliance and clinical outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT00857012.

Biweekly pegylated liposomal doxorubicin in patients with relapsed ovarian cancer: results of a multicenter phase-II trial.

BACKGROUND: The obvious benefit of pegylated liposomal doxorubicin (PLD) for tumour control in recurrent ovarian cancer is frequently offset by severe palmar-plantar erythrodysesthesia (PPE). There is evidence that dose reduction from 50 to 40 mg/m(2) reduces the incidence of PPE without compromising cytotoxic activity. We set out to investigate whether biweekly application further improves the therapeutic index of PLD. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after surgery and adjuvant chemotherapy with platinum and taxane compounds were eligible to participate in this multi-institutional phase II study. PLD was administered at a dose of 20 mg/m(2) every two weeks. Eligible patients had ECOG performance status of < or =2, and sufficient organ function. We employed an optimized two-stage design to test the hypothesis that biweekly application of PLD reduces the frequency of grade III and IV PPE from 25% to 10%. Response and survival were addressed descriptively. RESULTS: Between October 2001 and February 2004, 64 patients with median age of 59 (range 38-81) years were recruited onto this trial. We evaluated 553 (median 7, range 1-25) courses of PLD treatment. Most patients were in their third or fourth line of chemotherapy. PPE was noted in 30 patients (47.6%), but only three participants progressed to grade 3 severity (4.7%, 95% confidence interval 1.0-13.1%). Partial response, stable disease, and tumour progression were observed in 5, 13, and 24 patients, respectively. Median overall and progression-free survival were 18.2 (range, 1.4-34.0) and 4.3 (range 0.5-22.3) months. CONCLUSIONS: Biweekly PLD may reduce the incidence of PPE while retaining efficacy in relapsed ovarian cancer. Our data support the need for a randomized trial to strengthen these assumptions.

A phase II study of topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy.

BACKGROUND: Second-line chemotherapy for patients with ovarian cancer who failed platinum and paclitaxel treatment remains a therapeutic challenge. We investigated the toxicity profile and therapeutic efficacy of a novel combination regimen, topotecan plus gemcitabine, in a clinical phase II study. PATIENTS AND METHODS: Women with relapsed epithelial ovarian cancer after platinum and paclitaxel treatment were eligible to participate in this trial. Topotecan was given at an initial dose of 0.5 mg/m(2) daily (days 1-5), combined with gemcitabine 800 mg/m(2) and 600 mg/m(2) on days 1 and 8, respectively. Precluding good tolerability, this protocol facilitated subsequent dose increases of topotecan up to 1.0 mg/m(2). The primary objective was to determine the dose-limiting toxicity, whereas secondary objectives comprised measurable and CA-125 response rates, disease-free and overall survival. RESULTS: The twenty-one patients (median age 57 years, range 37-70 years) who were allocated to this trial received a total of 94 courses of chemotherapy. Median follow-up was 20.5 months. Topotecan dosage could be escalated to 0.75 mg/m(2) in nine patients and 1 mg/m(2) in another two patients. Dose reduction was not necessary in any case. There were no episodes of neutropenic fever, sepsis or chemotherapy-related fatalities. Only one patient developed CTC grade 4 leukopenia after the first treatment cycle, whereas three patients showed grade 3/4 anaemia. Five patients experienced thrombocytopenia grade 4 without clinical sequelae. Non-hematological toxicities were mild and rare. Eleven patients could be evaluated for clinical tumour response, with three complete, and four partial remissions. Two patients each had stable and progressive diseases. The median progression-free survival rate was 8.8 months [95% confidence interval (CI) 6.3-13.4 months]. The median overall survival rate was 21.1 months (95% CI 14.8-22.1 months). CONCLUSIONS: Topotecan combined with gemcitabine has a favourable toxicity profile and encouraging efficacy in patients with recurrent ovarian cancer.