Modified-BEP Chemotherapy in Patients With Germ-Cell Tumors Treated at a Comprehensive Cancer Center.

OBJECTIVES: Bleomycin, etoposide, and cisplatin (BEP) is the most common and successful chemotherapy regimen for germ-cell tumor (GCT) patients, accompanied by a bleomycin-induced dose-dependent lung toxicity in certain patients. In an attempt to reduce bleomycin-toxicity, we developed a modified-BEP (mBEP) regimen. MATERIALS AND METHODS: Between August 2008 and February 2018, 182 unselected mainly testicular GCT patients (39 with adjuvant purpose and 143 with curative purpose) received a tri-weekly 5-day hospitalization schedule with bleomycin 15 U intravenous (IV) push on day 1 and 10 U IV continuous infusion over 12 hours on days 1 to 3, cisplatin 20 mg/m IV, and etoposide 100 mg/m IV on days 1 to 5. Pulmonary toxicity was assessed through chest computed tomography scan and clinical monitoring. RESULTS: Median number of mBEP cycles was 3 (range: 1 to 4). In the curative setting, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic system, 112, 21, and 9 patients had good-risk, intermediate-risk, and poor-risk class, respectively; 66 (46%) patients had complete response (CR), 67 (47%) had partial response (52 of whom became CR afterwards), 6 (4%) had stable disease (that in 3 became CR afterwards), 3 (2%) progressed, and 1 (1%) died of brain stroke. At a median follow-up of 2.67 years (interquartile range: 1.23-5.00 y), 1 and 5-year overall survival and progression-free survival were 99% and 95%, and 90% and 88%, respectively. In the entire patient population, there was grade 3/4 neutropenia in 92 patients (51%), febrile neutropenia in 11 patients (6%), grade 1/2 nausea in 74 patients (41%), and no death due to pulmonary toxicity. CONCLUSION: In GCT patients, our mBEP-schedule would suggest an effective treatment modality without suffering meaningful pulmonary toxicity.

Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis.

Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusions.

Tumor infiltrating lymphocytes in gastrointestinal tumors: Controversies and future clinical implications.

Chronic inflammation following infections, autoimmune diseases or exposure to environmental irritants plays a crucial role in tumor development and influences the host immune response to neoplastic cells. The presence of an anti-tumor immune infiltrate is often associated with better outcomes in gastro-intestinal primary cancers, particularly in those with high microsatellite instability (MSI-H). Immunotherapeutic drugs inhibiting the PD-1 and PD-L1 pathway showed promising results in the treatment of these patients in the metastatic setting. The aim of this review is to resume the role tumor infiltrating lymphocytes (TILs) play in gastrointestinal tumors, underlining their potential value as a prognostic and predictive biomarker. TILs assessment could identify subsets of patients with high extent of TILs and better prognosis, that could be spared from adjuvant systemic treatments. Immune infiltration parameters might be additional predictors of a greater benefit from the immunotherapy with the immune checkpoint blockade.