No abstract

The objective of the analysis was to determine the effectiveness of re-treating patients with ovarian cancer, primary peritoneal cancer, and fallopian tube cancer with carboplatin after being deemed platinum resistant. From a database period January 1, 1996, to December 12, 2002, 34 patients were identified who received nonplatinum agents before resuming treatment with carboplatin. The median age was 65 years, and a median of two nonplatinum chemotherapy (range 1-5) prior to re-treatment with carboplatin was received. The median platinum-free interval from the time platinum was last received to re-treatment with carboplatin was 15.2 months (95% confidence interval [CI] 12.6-17.9; range 6.2-47.0). A median number of four cycles of carboplatin (range 1-11) was received. Two patients (5.9%) achieved partial response, while 21 patients (61.7%) achieved stable disease. The median time to progression for these 23 patients after re-treatment with carboplatin was 5.7 months (95% CI 5.2-6.3; range 1.8-15.3). Twenty-seven patients have died, and all patients have progressed. Seven patients are still receiving salvage therapy. The median overall survival from the time deemed to be platinum resistant is 23.2 months (95% CI 20.1-26.4). Patients who have been deemed platinum resistant may still benefit from platinum re-treatment after an interval of treatment with nonplatinum agents.

Despite advances in surgery and chemotherapy, less than 20% of patients with stage III or IV ovarian cancer survive long-term. In the past, cytotoxic regimens have been developed empirically, combining active agents at maximally tolerated doses, often without a clear rationale for their interaction. Advances in understanding the biology of ovarian cancer have identified multiple molecular targets that differ in normal and malignant cells. Targets include cell cycle regulators, growth factor receptors, signal transduction pathways, molecules that confer drug resistance, and angiogenic mechanisms. A number of targeted agents have entered clinical trials. Small molecular weight inhibitors, monoclonal antibodies, and antisense and gene therapy are all being evaluated alone and in combination with cytotoxic drugs. In contrast to earlier studies, the impact of each agent on the designated target can be assessed and agents can be matched to the genotype and phenotype of malignant and normal cells. In the long run, this should facilitate individualization of more effective, less toxic therapy for women with ovarian cancer.

We studied the immunohistochemical expression of HER-2/neu, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), estrogen receptor (ER), and progesterone receptor (PR) in uterine cervical small cell and large cell neuroendocrine carcinomas (SCNECs and LCNECs) from 24 patients seen at The University of Texas M.D. Anderson Cancer Center. The objectives were to determine their expression and prognostic role in survival. Twenty-three cases (95.8%) expressed VEGF. The tumors expressing EGFR, HER-2/neu, and COX-2 were modest in numbers: eight (33.3%), 10 (41.7%), and seven (29.2%), respectively. Only one tumor (4.2%) expressed ER, and only two tumors (8.3%) expressed PR. No significant differences in the expression of these factors were found between SCNECs and LCNECs or between stage I and stage II-III tumors. The median overall survival was 21.1 months (95% confidence interval [CI], 17.2-25.0 months). Only HER-2/neu expression was significantly associated with survival. Patients with negative HER-2/neu expression tumors had significantly shorter survival than those whose tumors were positive, 14.2 months (95% CI, 10.6-17.7 months) versus 33.1 months (95% CI, 0-76.92 months) (P = 0.03). There was a trend toward worse survival in patients with EGFR expression, but this finding was not significant. The combination of negative HER-2/neu expression and positive EGFR expression had the worst impact on survival.

We studied the immunohistochemical expression of HER-2/neu, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), estrogen receptor (ER), and progesterone receptor (PR) in uterine cervical small cell and large cell neuroendocrine carcinomas (SCNECs and LCNECs) from 24 patients seen at The University of Texas M.D. Anderson Cancer Center. The objectives were to determine their expression and prognostic role in survival. Twenty-three cases (95.8%) expressed VEGF. The tumors expressing EGFR, HER-2/neu, and COX-2 were modest in numbers: eight (33.3%), 10 (41.7%), and seven (29.2%), respectively. Only one tumor (4.2%) expressed ER, and only two tumors (8.3%) expressed PR. No significant differences in the expression of these factors were found between SCNECs and LCNECs or between stage I and stage II–III tumors. The median overall survival was 21.1 months (95% confidence interval [CI], 17.2–25.0 months). Only HER-2/neu expression was significantly associated with survival. Patients with negative HER-2/neu expression tumors had significantly shorter survival than those whose tumors were positive, 14.2 months (95% CI, 10.6−17.7 months) versus 33.1 months (95% CI, 0−76.92 months) (P = 0.03). There was a trend toward worse survival in patients with EGFR expression, but this finding was not significant. The combination of negative HER-2/neu expression and positive EGFR expression had the worst impact on survival.