Does a homeopathic medicine reduce hot flushes induced by adjuvant endocrine therapy in localized breast cancer patients? A multicenter randomized placebo-controlled phase III trial.

PURPOSE: Endocrine therapy (ET) used to reduce the risk of recurrence in hormone receptor-expressing disease (75% of breast cancers) is associated with worsening of climacteric symptoms with a negative impact on quality of life (QoL). Homeopathy might allow a better management of hot flushes (HF). METHODS: In this multicenter randomized double-blind placebo-controlled phase III study ( ClinicalTrials.gov NCT01246427), we enrolled ≥ 18 years old women with histologically proven non metastatic localized breast cancer, with Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≤ 1, treated for at least 1 month with adjuvant ET, and complaining about moderate to severe HF. Patients should not be scheduled for chemotherapy or radiotherapy, and had no associated pathology known to induce HF. After a 2- to 4-week placebo administration, we randomly assigned (1:1) patients with HFS ≥ 10 using an interactive web-based centralized platform to BRN-01 homeopathic medicine complex (Actheane®) in arm A or Placebo (Arm P). Randomization was stratified by adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS) were calculated as the mean of HF frequencies before randomization, at 4, and at 8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity scale. Primary endpoint was assessed at 4-week post-randomization, as the variation between pre- and 4w-HFS. Secondary endpoints included HFS variation between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after randomization, and QoL and satisfaction assessed at 4- and 8-week post-randomization. RESULTS: Two hundred ninety-nine patients were included, and 138 (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, - 2.9; P, - 2.5 points, p = 0.756) and relative decrease (A, - 17%; P, - 15%, p = 0.629) were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs 48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43 (72%) vs 51 (74%) patients (p = 0.470). CONCLUSIONS: The efficacy endpoint was not reached, and BRN-01 administration was not demonstrated as an efficient treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients. However, the study drug administration led to decreased HFS with a positive impact on QoL. Without any recommended treatment to treat or alleviate the HF-related disabling symptoms, Actheane® could be a promising option, providing an interesting support for better adherence to ET, thereby reducing the risk of recurrence with a good tolerance profile.

Final results of ERASME-4: a randomized trial of first-line docetaxel plus either capecitabine or epirubicin for metastatic breast cancer.

OBJECTIVE: To assess the efficacy of capecitabine plus docetaxel (XT) versus epirubicin plus docetaxel (ET) as first-line therapy for metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients with no prior chemotherapy for MBC were randomized to 3-weekly cycles of either XT (capecitabine 1,000 mg/m(2) twice daily, days 1-14; docetaxel 75 mg/m(2), day 1) or ET (epirubicin 75 mg/m(2), day 1; docetaxel 75 mg/m(2), day 1). The primary endpoint was non-progression rate 6 months after randomization. The planned sample size was 106 patients based on a randomized, phase II selection design. RESULTS: Between April 2004 and January 2007, 68 patients were randomized, giving 82% power to select the best regimen according to a 6-month non-progression rate. Slow accrual led to premature study termination. Baseline characteristics were generally well balanced between arms. The 6-month non-progression rates were 75.8% with XT versus 65.7% with ET (p = 0.36). After 42 months' median follow-up, median progression-free survival was 12.4 versus 6.8 months, respectively (p = 0.040). The safety profiles were consistent with previous experience. CONCLUSION: Further larger studies are warranted to validate these results. Despite more grade 3 hand-foot syndrome, first-line XT may be a valid alternative to ET, potentially improving efficacy.

Epirubicin and paclitaxel (EPI-TAX regimen) for advanced ovarian cancer after failure of platinum-containing regimens.

BACKGROUND: The place of anthracyclines in the treatment of advanced ovarian cancer remains a matter of debate. We have assessed the feasibility and evaluated the tolerance of epirubicin (EPI) combined with paclitaxel (TAX) in heavily pretreated ovarian cancer patients. METHODS: Between March 1996 and March 1998, 34 patients with ovarian cancer in relapse after platinum-based chemotherapy received EPI (75 mg/m(2)/day, iv) and TAX (175 mg/m(2)/day, 3-h infusion). Cycles were repeated every 3 weeks. This treatment was second-line for 10 patients and third/fourth-line for 24. RESULTS: Of the 34 assessable patients, 15 (44%) (95% confidence interval 27-60%) achieved objective response (3 complete and 12 partial responses). The number of previous lines of chemotherapy or previous anthracycline treatments did not influence response rates. Responders to previous paclitaxel-based regimens had a significantly higher response rate to EPI-TAX combination (57%) than nonresponders (11%) (P = 0.05). Median response duration was 40 weeks (range 12-94). Median survival from inclusion was 10.7 months (range 1-40). Myelosuppression was the most frequent side effect. Grade 3/4 neutropenia occurred in 31 patients (91%), febrile neutropenia episodes in 17%, and grade 3/4 anemia and thrombopenia in 27 and 24%, respectively. The main nonhematological toxicities included alopecia and grade 2 peripheral neuropathy (12%). Cardiac dysfunction was observed in one patient after the fourth treatment cycle. CONCLUSIONS: Toxicity of the EPI-TAX regimen was acceptable in this population of heavily pretreated ovarian cancer patients. The regimen was effective and it is considered an option for patients previously responding to paclitaxel-based therapy.