Multicenter phase 2 study of combined gemcitabine and epirubicin as second-line treatment for patients with advanced ovarian cancer.

OBJECTIVE: The aim of this phase 2 trial was to evaluate the tolerability and efficacy of combined gemcitabine (G) and epirubicin (E) as second-line treatment for patients with advanced ovarian cancer. METHODS: Treatment with G 1000 mg/m2 (days 1 and 8) and E 60 mg/m2 (day 1) every 3 weeks for 3 or, in the absence of progression, 6 courses. RESULTS: Fifty patients with advanced ovarian cancer (31 serous, 2 endometrioid, 10 unclassified adenocarcinoma, and 7 other) and a median age of 60 years (range, 38-74 years) were enrolled after giving their informed consent. Performance status according to the Eastern Cooperative Oncology Group was 0 in 29 patients (58%), 1 in 17 patients (34%), and 2 in 4 patients (8%), and the initial stages according to the International Federation of Gynecology and Obstetrics were I to II in 4 patients (8%), III in 31 patients (62%), and IV in 15 patients (30%). They had previously received a median of 1.5 lines of treatment (range, 1-4). The median platinum-free interval was 5 months (range, 0-12 months): 32 patients had relapse within 6 months and 18 patients had relapse after 6 months. The response rate was 42% (2% complete response and 40% partial response), with a median duration of 7.2 months: the corresponding figures were 37.5% and 5.2 months in the platinum-resistant patients and 50% and 8.8 months in the platinum-sensitive patients. The main grade 3 to 4 hematological toxicity was neutropenia (56% of cases). After a median follow-up of 13.5 months, median progression-free survival was 5 months, and median overall survival was 23.5 months. CONCLUSIONS: This E + G combination seems to be active and safe in platinum-resistant/refractory patients.

M-CAM expression as marker of poor prognosis in epithelial ovarian cancer.

Currently available clinico-pathologic criteria provide an imperfect assessment of outcome for patients with advanced epithelial ovarian cancer (EOC). Identification of prognostic factors related to tumor biology might improve this assessment. We investigated the prognostic significance of the melanoma cell adhesion molecule (M-CAM) in EOC. Using the same antibody, M-CAM expression was tested by Western blotting in protein extracts and by immunohistochemestry in tissue microarrays generated from 133 consecutively resected, well characterized EOC samples. Fisher test, Kaplan-Meier method and Cox proportional hazards analysis were used to relate M-CAM expression to clinico-pathological variables and to time to progression (TTP) and overall survival (OS). In vitro biochemical analysis showed a progressively increased M-CAM expression from normal to malignant cells. M-CAM protein, detected immunohistochemically, was significantly associated with advanced tumor stage, serous and undifferentiated histotype, extent of residual disease and p53 accumulation. Presence or absence of M-CAM significantly divided patients according to their TTP (median, 22 vs. 79 months, respectively; log-rank p = 0.001) and OS (median, 42 vs. 131 months, respectively; log-rank p = 0.0003). In the subgroup of advanced stage patients who achieved complete response after front-line treatment, M-CAM expression and absence of residual disease were significantly associated with shorter TTP (p = 0.003, HR 5.25, 95% Cl 1.79-15.41 and p = 0.011, HR 3.77, 95% Cl 1.36-10.49 respectively) at the multivariate level. In the same sub-group of patients, M-CAM expression remained the only parameter significantly associated with OS (p = 0.005, HR 3.35, 95% Cl 1.42-6.88). M-CAM is a marker of early relapse and poorer outcome in EOC. In particular, M-CAM expression identifies a subgroup of front-line therapy-responding patients who undergo dramatic relapses, thus helping to better select patients who might benefit from new/alternative therapeutic modalities.

Detecting cell-free circulating hTERT mRNA in the plasma may identify a subset of nonsmall cell lung cancer patients.

Human telomerase reverse transcriptase (hTERT), the catalytic subunity of telomerase, a marker of cell immortalization, is upregulated in most tumors, including nonsmall cell lung cancer (NSCLC). However, little is known about the role of assessing cell-free plasma circulating hTERT mRNA for tracing these tumors. We investigated by RT-polymerase chain reaction (PCR) and real-time quantitative PCR the prevalence and functional implications of hTERT mRNA in both tumor tissue and paired plasma samples in 34 (27 males and 7 females) stages I-IIIB NSCLC patients (21 adenocarcinomas and 13 squamous-cell carcinomas) by using intron- and exon-spanning primers. Plasma samples of ten healthy volunteers and normal lung tissue were used as negative controls. We detected hTERT mRNA in the plasma of 4 out of 34 (12%) tumor patients, but none was detected in the ten plasma samples of healthy volunteers. Normal lung tissue was completely devoid of hTERT mRNA. No association was found between hTERT plasma mRNA and clinicopathologic variables of the patients' population. We conclude that cell-free circulating hTERT mRNA is detectable in a subset of patients, whereas it is consistently absent in healthy volunteers. It can be added to the panel of multiple genetic tracers to detect lung cancer in the plasma of patients, although, per se, it is not specific for this tumor.