Alopecia as surrogate marker for chemotherapy response in patients with primary epithelial ovarian cancer: a metaanalysis of four prospective randomised phase III trials with 5114 patients.

PURPOSE: Alopecia is a common side-effect of chemotherapy and affects quality of life of cancer patients. Some patients and physicians believe that alopecia could be a surrogate marker for response to chemotherapy and impact on prognosis. However, this was never been tested in a sufficiently large cohort of ovarian cancer patients. PATIENTS AND METHODS: We analysed retrospectively the meta-databank of four prospective randomised phase-III-trials with platinum- and taxane-based 1st-line-chemotherapy in patients with advanced epithelial ovarian cancer (EOC) regarding the impact of alopecia overall outcome. RESULTS: For 4705 (92.0%) of a total of 5114 EOC-patients alopecia was documented. They had received on median six cycle platinum-taxane chemotherapy (range 0-11) with 4186 (89.0%) having completed ⩾ 6 cycles. Worst alopecia grade was 0 in 2.4%, 1 in 2.9% and 2 in 94.7% of the patients. In a univariate analysis, including all patients, grade-0/1 alopecia was associated with significantly lower progression free survival (PFS) and overall survival (OS) compared to grade-2 alopecia. However when assessing only those patients who completed ⩾ 6 chemotherapy-cycles and hence eliminating the bias of lower total dose of treatment, alopecia failed to retain any significant impact on survival in the multivariate analysis. Merely the time point of alopecia onset was an independent prognostic factor of survival: patients who developed grade-2 alopecia up to cycle 3 had a significantly longer OS compared to patients who experienced alopecia later during therapy (hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.04-1.50). CONCLUSIONS: Within a large EOC-patient cohort with 1st-line platinum- and taxane-based chemotherapy early onset alopecia appears to be significantly associated with a more favourable outcome in those patients who completed ⩾ 6 chemotherapy cycles. It remains to be elucidated if early onset alopecia is just a surrogate marker for higher sensitivity to chemotherapy or if other biological effects are underlying.

Bevacizumab in heavily pre-treated and platinum resistant ovarian cancer: a retrospective study of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) Ovarian Cancer Study Group.

BACKGROUND: Bevacizumab is an agent with a tolerable safety profile which was described to be effective in recurrent ovarian cancer in recent phase I and phase II trials. But it remains unclear if these characteristics can translate to the very special collective of heavily pre-treated ovarian cancer patients. The present analysis was conducted to answer questions regarding safety and efficacy for the use of bevacizumab in these patients. PATIENTS AND METHODS: A single-center, retrospective chart review was performed including all patients with histologically confirmed ovarian cancer and treatment with bevacizumab between 1981 and 2008. Data documentation was performed with an internet-based documentation tool (Alcedis Med, Alcedis, Gießen, Germany). All data were analyzed using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). RESULTS: Overall, 15 patients who were treated with bevacizumab outside of a clinical study were identified. A total of 134 cycles of bevacizumab were applied, with a median of 8.9 cycles per patient. All 15 patients had platinum-resistant disease at the time of treatment, with a median of 5.4 prior lines of chemotherapy (range 1-7). The best response under treatment with bevacizumab was classified as partial response in 2 patients (13.3%). Stable disease was found in 6 (40%) and progressive disease in 7 (46.7%) patients. The median time to progression was 6.6 months and the median overall survival was 15.0 months from the first cycle of bevacizumab. At the time of analysis 3 patients were still alive and 1 patient had been lost to follow-up. No gastrointestinal perforations or treatment related deaths were observed. Severe adverse events included 3 fistulas (20%), 1 impaired wound healing (6.6%) and 1 severe blood pressure crisis (6.6 %). DISCUSSION: Despite previous experience of a high rate of bowel perforations in patients with ovarian cancer treated with bevacizumab, no perforation was observed in this analysis despite the fact that this collective was a heavily pretreated and platinum resistant subgroup. The most severe possible side effect in this group was the occurrence of fistula, which might suggest that bevacizumab is a therapy option with an acceptable safety profile, even though the rate of fistulas is higher than reported in previous studies. This might again be related to the nature of this very special subgroup of heavily pretreated patients. CONCLUSION: The results of this analysis suggest that bevacizumab might be an efficient therapy option in the setting of heavily pre-treated ovarian cancer with a tolerable safety profile even in this very special collective.