Purpose: Inflammation indexes and body mass index (BMI) are easily evaluated, predict survival, and are potentially modifiable. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of patients with renal cell carcinoma (RCC) undergoing immune checkpoint inhibitor therapy. Experimental Design: A prospective cohort of patients with metastatic RCC treated with nivolumab enrolled in the Italian Expanded Access Program from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil-to-lymphocyte ratio (NLR) </≥ 3, systemic immune inflammation index (SII) </≥ 1,375, and platelet-to-lymphocyte ratio (PLR) </≥ 232. Patients were classified as high BMI (≥25 kg/m2) versus normal BMI (<25 kg/m2). Results: Among 313 evaluable patients, 235 (75.1%) were male, and median age was 65 years (range, 40–84 years), with 105 (33.69%) ≥70 years. In univariate analysis, age, performance status, BMI, SII, NLR, and PLR were able to predict outcome. In multivariate analyses, SII ≥1,375, BMI <25 kg/m2, and age ≥70 years independently predicted overall survival [OS; HR = 2.96, 95% confidence interval (CI), 2.05–4.27; HR = 1.59, 95% CI, 1.10–2.30; and HR = 1.65, 95% CI, 1.07–2.55, respectively). A patient with both SII ≥1,375 and BMI <25 kg/m2 was estimated to have much worse OS (HR, 3.37; 95% CI, 2.29–4.95; P <0.0001) than a patient with neither or only one risk factor. SII changes at 3 months predicted OS (P <0.0001). Conclusions: Normal BMI combined with inflammation tripled the risk of death, suggesting that these biomarkers are critical prognostic factors for OS in patients with RCC treated with nivolumab.

Purpose Unresponsiveness to erythropoiesis-stimulating agents, occurring in 30% to 50% of patients, is a major limitation to the treatment of chemotherapy-related anemia. We have prospectively evaluated whether intravenous iron can increase the proportion of patients with chemotherapy-related anemia who respond to darbepoetin. Patients and Methods Between December 2004 and February 2006, 149 patients with lung, gynecologic, breast, and colorectal cancers and ≥ 12 weeks of planned chemotherapy were enrolled from 33 institutions. Patients were required to have hemoglobin ≤ 11 g/L and no absolute or functional iron deficiency. All patients received darbepoetin 150 μg subcutaneously once weekly for 12 weeks and were randomly assigned to sodium ferric gluconate 125 mg intravenously (IV) weekly for the first 6 weeks (n = 73) or no iron (n = 76). Primary end point of the study was the percentage of patients achieving hematopoietic response (hemoglobin ≥ 12 g/dL or ≥ 2 g/dL increase). Results Hematopoietic respon...

Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor. Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m ² , on days 1 and 5], epirubicin [30 mg/m ² , days 1 and 5], L -leucovorin [100 mg/m ² , days 1–4], and 5-fluorouracil [300 mg/m ² , days 1–4] in a hospital setting. Frequencies and severity of adverse events were determined. Overall survival (OS) and disease-free survival (DFS) were compared between the treatment arms using Kaplan–Meier analysis and a Cox proportional hazards regression model. All statistical tests were two-sided. From January 1995 through September 2000, 258 patients were randomly assigned to chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were well balanced between the two arms. Among those who received chemotherapy, grade 3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of patients, respectively. After a median follow-up of 72.8 months, 128 patients (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity-related. Relative to treatment with surgery alone, adjuvant chemotherapy did not increase disease-free survival (hazard ratio [HR] of recurrence = 0.92 ; 95% confidence interval [CI] = 0.66 to 1.27) or overall survival (HR of death = 0.90; 95% CI = 0.64 to 1.26). Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival. The estimated effect of chemotherapy (10% reduction in the hazard of death or relapse) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents.

Background: In advanced colorectal cancer, chemotherapy is usually administered without pauses and until progression but patients can experience cumulative toxicity and cannot tolerate a heavy therapeutic charge. Aim: The aim of the present trial was to evaluate whether an intermittent chemotherapy with levo-leucovorin + 5-fluorouracil (5-FU) + irinotecan (CPT-11) was at least as effective as the same regimen given continuously, both administered until progression, in patients affected with advanced colorectal cancer and not previously exposed to chemotherapy for metastatic disease. Patients, materials and methods: A total of 337 patients from 27 institutions were randomised between levo-leucovorin, 100/mg/m² i.v. + 5-FU; 400 mg/m² i.v. bolus + 5-FU; 600 mg/m² 22-h continuous infusion, days 1 and 2 + CPT-11; 180 mg/m² day 1, administered every 2 weeks 2 months on and 2 months off (arm A) and the same regimen administered continuously (arm B), until progression in both arms. The main end point was overall survival (OS), the secondary progression-free survival (PFS) and toxicity. Results: At a median follow-up of 41 months, OS was 18 months in arm A and 17 months in arm B [hazard ratio (HR), 0.88]. Also PFS was comparable in the two groups (6 months in both, with HR, 1.03), and even grades 3–4 toxicity (mainly myelosuppression, fever and diarrhoea) was similar. Second-line oxaliplatin-based treatment was administered in a similar percentage (66%) in the two arms. The median chemotherapy-free period (drug holiday) in arm A was 3.5 months. Conclusion: Reducing the charge of therapy in this population did not diminish the efficacy of treatment. Further studies with this strategy, including biologicals, are warranted.

Backgroud: Germ cell tumors (GCTs) are a group of neoplasms usually arising in the gonads, and very rarely in sites outside the gonads, mainly in the retroperitoneum, the anterior mediastinum, and pineal gland or the coccyx (mainly in childhood). The prognosis of nonseminoma primary mediastinal GCTs (PMGCTs), is considered to be poorer compared to its retroperitoneal or gonadal counterparts and, according to the International Germ Cell Cancer Collaborative Group, it is considered by definition as a “poor risk” disease. Material and Methods Our review highlights the clinical features, prognostic factors, and therapeutic strategies in PMGCTs, as described in medical literature. So far available data were obtained through a Medline search of English-language papers. Results: Due to the rarity of the disease, there are no prospective studies comparing different treatment strategies. For this reason, oncology societies recommend treating PMGCTs like other GCTs, according to general risk categories. Conclusion: Because of the rarity of the disease, poor categorization, and the lack of novel therapeutic strategies, an International database is required to obtain more information on these tumors. Additional efforts should be done, with the aims to find effective novel therapeutic agents.