A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN.

BACKGROUND: Avastin and Roferon in Renal Cell Carcinoma (AVOREN) demonstrated efficacy for bevacizumab plus interferon-α2a (IFN; 9 MIU tiw) in first-line metastatic renal cell carcinoma (mRCC). We evaluated bevacizumab with low-dose IFN in mRCC to determine whether clinical benefit could be maintained with reduced toxicity. METHODS: BEVLiN was an open-label, single-arm, multinational, phase II trial. Nephrectomized patients with treatment-naive, clear cell mRCC and favourable/intermediate Memorial Sloan-Kettering Cancer Center scores received bevacizumab (10 mg/kg every 2 weeks) and IFN (3 MIU thrice weekly) until disease progression. Descriptive comparisons with AVOREN patients having favourable/intermediate MSKCC scores treated with bevacizumab plus IFN (9 MIU) were made. Primary end points were grade ≥3 IFN-associated adverse events (AEs) and progression-free survival (PFS). All grade ≥3 AEs and bevacizumab/IFN-related grade 1-2 AEs occurring from first administration until 28 days after last treatment were reported. RESULTS: A total of 146 patients were treated; the median follow-up was 29.4 months. Any-grade and grade ≥3 IFN-associated AEs occurred in 53.4% and 10.3% of patients, respectively. The median PFS and overall survival were 15.3 [95% confidence interval (CI): 11.7-18.0] and 30.7 months (95% CI: 25.7-not reached), respectively. The ORR was 28.8%. CONCLUSIONS: Compared with a historical control AVOREN subgroup, low-dose IFN with bevacizumab resulted in a reduction in incidence rates of IFN-related AEs, without compromising efficacy [NCT00796757].

Initial results of a randomized controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short-course radiotherapy or long-term chemoradiotherapy, both with delayed surgery.

AIM: The aim of this study was to compare the downstaging achieved after long-course chemoradiotherapy (chRT) and short-term radiotherapy (sRT) followed by delayed surgery. METHOD: A randomized controlled trial was carried out. Eighty-three patients with resectable stage II and III rectal adenocarcinoma were randomized to receive long-course chemoradiotherapy (46) and short-term radiotherapy (5×5 Gy) (37). Surgery was performed 6 weeks after preoperative treatment in both groups. RESULTS: The R0 resection rate was 91.3% in the chRT and 86.5% in the sRT group (P=0.734). Sphincter preservation rates were 69.6%vs 70.3% (P=0.342) and postoperative complication rates were 26.1%vs 40.5% (P=0.221). There were more patients with early pT stage [pT0 (complete pathological response) pT1] in the chRT group [21.8%vs 2.7% (P=0.03)] and more patients with pT3 disease in the sRT group [75.7%vs 52.2% (P=0.036)]. There were no differences in pN stage and lymphatic or vascular invasion in either group. Pathological downstaging (stage 0 and I) was observed in eight (21.6%) patients in the sRT group and in 18 (39.1%) in the chRT group (P=0.07). Tumours were smaller after preoperative ChRT (2.5 cm vs 3.3 cm; P=0.04). CONCLUSION: Long-course preoperative chemoradiation resulted in greater statistically significant tumour downsizing and downstaging compared with short-term radiation, but there was no difference in the R0 resection rates. Similar postoperative morbidity was observed in each group.

Oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer - A EURECCA international comparison between the Netherlands, Belgium, Denmark, Sweden, England, Ireland, Spain, and Lithuania.

INTRODUCTION: The aim of this EURECCA international comparison is to compare oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer between European countries. MATERIAL AND METHODS: Population-based national cohort data from the Netherlands (NL), Belgium (BE), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), Spain (ES), and single-centre data from Lithuania (LT) were obtained. All operated patients with (y)pTNM stage I-III rectal cancer diagnosed between 2004 and 2009 were included. Oncologic treatment strategies and relative survival were calculated and compared between neighbouring countries. RESULTS: We included 57,120 patients. Treatment strategies differed between NL and BE (p < 0.001), DK and SE (p < 0.001), and ENG and IE (p < 0.001). More preoperative radiotherapy as single treatment before surgery was administered in NL compared with BE (59.7% vs. 13.1%), in SE compared with DK (55.1% vs. 10.4%), and in ENG compared with IE (15.2% vs. 9.6%). Less postoperative chemotherapy was given in NL (9.6% vs. 39.1%), in SE (7.9% vs. 14.1%), and in IE (12.6% vs. 18.5%) compared with their neighbouring country. In ES, 55.1% of patients received preoperative chemoradiation and 62.3% postoperative chemotherapy. There were no significant differences in relative survival between neighbouring countries. CONCLUSION: Large differences in oncologic treatment strategies for patients with (y)pTNM I-III rectal cancer were observed across European countries. No clear relation between oncologic treatment strategies and relative survival was observed. Further research into selection criteria for specific treatments could eventually lead to individualised and optimal treatment for patients with non-metastasised rectal cancer.

Adjuvant chemotherapy and relative survival of patients with stage II colon cancer - A EURECCA international comparison between the Netherlands, Denmark, Sweden, England, Ireland, Belgium, and Lithuania.

BACKGROUND: The aim of the present EURECCA international comparison is to compare adjuvant chemotherapy and relative survival of patients with stage II colon cancer between European countries. METHODS: Population-based national cohort data (2004-2009) from the Netherlands (NL), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), and Belgium (BE) were obtained, as well as single-centre data from Lithuania. All surgically treated patients with stage II colon cancer were included. The proportion of patients receiving adjuvant chemotherapy was calculated and compared between countries. Besides, relative survival was calculated and compared between countries. RESULTS: Overall, 59,154 patients were included. The proportion of patients receiving adjuvant chemotherapy ranged from 7.1% to 29.0% (p < 0.001). Compared with NL, a better adjusted relative survival was observed in SE (stage II: relative excess risks (RER) 0.53, 95% confidence interval (CI) 0.44-0.64; p < 0.001), and BE (stage II: RER 0.84, 95% CI 0.76-0.92; p < 0.001), and in IE for patients with stage IIA disease (RER 0.80, 95% CI 0.65-0.98; p = 0.03). CONCLUSION: The proportion of patients with stage II colon cancer receiving adjuvant chemotherapy varied largely between seven European countries. No clear linear pattern between adjuvant chemotherapy and adjusted relative survival was observed. Compared with NL, SE and BE showed an improved adjusted relative survival for stage II disease, and IE for patients with stage IIA disease only. Further research into selection criteria for adjuvant chemotherapy could eventually lead to individually tailored, optimal treatment of patients with stage II colon cancer.