Improvement in survival and quality of life with new therapeutic agents in metastatic castration-resistant prostate cancer: comparison among the results.

Androgen deprivation therapy is the mainstay of treatment for men affected by metastatic prostate cancer (PC). Unfortunately, nearly all patient will become resistant to the initial hormonal approach, developing a metastatic castration-resistant prostate cancer (mCRPC). For many years, chemotherapy with docetaxel has been the only established standard of care for men with mCRPC. Recent developments in the knowledge of the disease biology have shown that during the progression to the castrate status PC remains dependent on androgens and androgen receptor (AR) pathway. As a consequence, new agents like abiraterone acetate and enzalutamide have been rapidly developed and approved for clinical use. Other drugs with different mechanisms of action, such as sipuleucel-T, cabazitaxel, and radium-223 have shown to improve overall survival, symptom control and quality of life of mCRPC patients. However, the optimal sequencing and combination of these treatments are not defined yet. Studies on biomarkers for treatment selection, such as AR splice variants, are promising, but the initial data still need prospective validation on large patient series.

Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?

BACKGROUND: Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. PATIENTS AND METHODS: We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy. RESULTS: Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in four patients (10.2%). Median progression-free survival was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (P = 0.01). CONCLUSION: Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options.

Clinical and molecular determinants of survival in pancreatic cancer patients treated with second-line chemotherapy: results of an Italian/Swiss multicenter survey.

BACKGROUND: Increased knowledge about the treatment of pancreatic cancer has influenced the management of locally advanced and metastatic disease. Nonetheless, prognosis remains dismal (24%, 1-year survival). The impact on overall survival (OS) of second-line therapy has not been clarified and the use of platinum salts and/or fluoropyrimidines is hotly debated. It is the hope that future treatment can be tailored to predict chemosensitivity in order to improve outcomes in patients with locally advanced and metastatic pancreatic cancer. Since DNA-damaging agents could be one therapeutic option, a retrospective multicenter study was performed to evaluate the efficacy of salvage treatment with the hypothesis that levels of the DNA repair gene excision repair cross complementing 1 (ERCC1) could influence OS. PATIENTS AND METHODS: In a population of 160 patients treated with fluoropyrimidine-based second-line chemotherapy, expression levels of ERCC1 were determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). In 108 patients with locally advanced and metastatic pancreatic cancer treated with either fluoropyrimidines and platinum salts (group A=58) or fluoropyrimidines alone (group B=50), ERCC1 levels were correlated with OS, time to progression and response to chemotherapy. RESULTS: Median survival was significantly higher in group A with low ERCC1 levels [11.9 versus 9.9 months; p ≤ 0.05] (median follow-up 24 months). Moreover in the same group, a trend towards longer time to progression was observed. No differences in OS were observed when ERCC1 was studied (low versus high) in patients not treated with platinum salts. On multivariate analysis of pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for OS. CONCLUSION: The results of this study indicate that ERCC1 may predict survival in pancreatic cancer patients treated by platinum and fluoropyrimidine as second-line chemotherapy.