Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer.

BACKGROUND: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. METHODS: Patients were randomised (2 : 1) to IMM-101 (10 mg ml(-l) intradermally)+GEM (1000 mg m(-2) intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. RESULTS: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44-1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33-0.87, P=0.01). CONCLUSIONS: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.

Value of multi-disciplinary input into laparoscopic management of rectal cancer - An observational study.

AIM: To assess the impact of multi-disciplinary teams (MDTs) management in optimising the outcome for rectal cancers. METHODS: We undertook a retrospective review of a prospectively maintained database of patients with rectal cancers (defined as tumours ≤ 15 cm from anal verge) discussed at our MDT between Jan 2008 and Jan 2011. The data was validated against the national database to ensure completeness of dataset. The clinical course and follow-up data was validated using the institution's electronic patient records. The data was analysed in terms of frequencies and percentages. Significance of any differences were analysed using χ2 test. A Kaplan-Meier analysis was performed for overall survival and disease free survival. RESULTS: Following appropriate staging, one hundred and thirty-three patients were suitable for potentially curative resections. Seventy two (54%) were upper rectal cancer (URC) - tumour was > 6 cm from the anal verge and 61 (46%) were lower rectal cancers (LRC) - lower extent of the tumour was palpable ≤ 6 cm. Circumferential resection margin (CRM) appeared threatened on pre-operative MRI in 19/61 (31%) patients with LRC requiring neo-adjuvant therapy (NAT). Of the 133 resections, 118 (89%) were attempted laparoscopically (5% conversion rate). CRM was positive in 9 (6.7%) patients; Median lymph node harvest was 12 (2-37). Major complications occurred in 8 (6%) patients. Median follow-up was 53 mo (0-82). The 90-d mortality was 2 (1.5%). Over the follow-up period, disease related mortality was 11 (8.2%) and overall mortality was 39 (29.3%). Four (3%) patients had local recurrence and 22 (16.5%) patients had distant metastases. CONCLUSION: Management of rectal cancers can be optimized with multi-disciplinary input to attain acceptable long-term oncological outcomes even when incorporating a laparoscopic approach to rectal cancer resection.