Impact of age and gender on the efficacy and safety of upfront therapy with panitumumab plus FOLFOX followed by panitumumab-based maintenance: a pre-specified subgroup analysis of the Valentino study.

BACKGROUND: The safety and efficacy outcome of elderly metastatic colorectal cancer (mCRC) patients fit enough to receive combination chemotherapy plus biological agents is an issue of growing interest. Also, gender-specific differential toxicity and efficacy of anti-epidermal growth factor receptor (EGFR)-based upfront treatments need to be explored. PATIENTS AND METHODS: Valentino was a multicenter, randomized, phase II trial, investigating two panitumumab-based maintenance strategies following first-line panitumumab plus FOLFOX in RAS wild-type mCRC patients. We carried out a subgroup analysis, aimed at assessing the differences in efficacy, safety and quality of life (QoL) according to age (<70 versus ≥70 years) and gender (male versus female). Efficacy endpoints were progression-free survival (PFS), overall survival (OS) and overall response rate (ORR); safety endpoints were rates of any grade and grade 3/4 adverse events (AEs). RESULTS: No significant differences in terms of PFS, OS and ORR were observed between patients aged <70 or ≥70 years and the effect of the maintenance treatment arm on survival outcomes was similar in the two subgroups. The safety profile of both induction and maintenance treatment and the impact on QoL were similar in elderly and younger patients. No significant differences in PFS, OS, ORR or clinical benefit rate were observed according to gender. A significantly higher rate of overall grade 3/4 AEs (P = 0.008) and of grade 3/4 thrombocytopenia (P = 0.017), any grade and grade 3/4 neutropenia (P < 0.0001) and any grade conjunctivitis (P = 0.033) was reported in female as compared to male patients. Conversely, we reported a significantly higher incidence of any grade skin rash (P = 0.0007) and hypomagnesemia (P = 0.029) in male patients. CONCLUSIONS: The upfront choice of an anti-EGFR-based doublet chemotherapy followed by a maintenance strategy represents a valuable option in RAS wild-type mCRC irrespective of gender and age, though a careful evaluation of patients to maximize the risk/benefit ratio is warranted.

Supportive care needs, quality of life and psychological morbidity of advanced colorectal cancer patients.

PURPOSE: This study describes the supportive care needs in a consecutive sample of Italian colorectal cancer (CRC) patients, evaluating their quality of life and psychological morbidity. METHODS: This study used a cross-sectional design and self-assessment procedures and was conducted in an ambulatory setting. Demographics, basic clinical features, supportive care needs, quality of life and psychological morbidity of 203 CRC patients were gathered. RESULTS: Approximately the 80% of the patients experienced one or more moderate- or high-level unmet need, notably regarding psychological concerns (approximately the 20% presented also signs of anxiety and depression). Functional roles and cognitive functioning were low. Symptoms of fatigue, nausea and vomiting and financial issues were frequent. The severity of anxiety, depression and quality of life impairment was significantly different across different levels of needs according to a unique linear relation. Patients with moderate or high needs had more severe anxiety and depression and a lower quality of life (i.e., lower level of functioning and more severe symptoms) than those with no needs or low needs. CONCLUSIONS: The findings of this study suggest that meeting supportive care needs seems to improve psychological morbidity, functions and symptoms of CRC patients.

Phase II study of cisplatin, gemcitabine and 5-fluorouracil in advanced pancreatic cancer.

BACKGROUND: The aim of this study was to determine the activity of the combination of cisplatin, gemcitabine and 5-fluorouracil (5-FU) as therapy for metastatic or locally advanced inoperable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic pancreatic adenocarcinoma received first-line chemotherapy comprising cisplatin (20 mg/m2 on days 1, 8, 15, 22, 29 and 36), gemcitabine (1000 mg/m2 on days 1, 8, 29 and 36) and 5-FU (200 mg/m2 as continuous infusion on days 1-42) every 56 days. RESULTS: A total of 34 patients were studied. Eighty courses were administered (median two courses per patient). Among 32 patients evaluable for response, two patients had a complete response and four a partial response for an overall response rate of 19% (95% confidence interval 7% to 36%). Thirteen patients had stable disease (40%) and 13 progressed. Median progression-free survival was 4.7 months, median survival 9.0 months and 26% of patients achieved 1-year survival. Ten of 25 patients (40%) with pain at presentation had a sustained reduction of analgesic consumption. The principal grade 3/4 toxicities were neutropenia, thrombocytopenia, anaemia and mucositis, occurring in 24%, 21%, 9% and 3% of patients. CONCLUSION: This schedule seems well tolerated and active in pancreatic cancer and worthwhile of further evaluation.

Low dose carboplatin (AUC 4.5) combined with vinorelbine in the treatment of advanced non-small cell lung cancer: a single institution phase II study.

Platinum compounds and vinorelbine (VNB) are active in the treatment of non-small cell lung cancer (NSCLC), but moderate toxicity has been reported. The aims of the present study were to assess activity and tolerability of low dose carboplatin (CBDCA): 4.5 AUC according to Calvert formula on day 1, combined with vinorelbine: 25 mg/m2 on days 1 and 8, administered every 4 weeks. Eighty-five advanced NSCLC patients entered the study; all of them were evaluable for toxicity and 83 were evaluable for activity. According to an intent to treat analysis, 26 patients attained a partial response (30.5%; 95% CI 20.5-40.5), 27 (31.7%) obtained a disease stabilization and 30 (35%) progressed. This regimen appeared to be modestly toxic, grade 3-4 leukopenia and thrombocytopenia were observed in less than 5% of cases and grade 2 neuropathy in 10% of cases. Median time to progression and overall survival were 7 and 9 months, respectively. In conclusion, low dose CBDCA (administered following Calvert's formula) and VNB combination is an active and very well tolerated cytotoxic regimen in the treatment of advanced NSCLC. The application of the Calvert formula may have contributed to limit the side effects related to CBDCA.