Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: the BIBABRAX study.

PURPOSE: To evaluate the health-related quality of life (HRQoL), global health status (GHS), and deterioration-free survival of an elderly population (> 70 years) with unresectable locally advanced (LAPC) or metastatic pancreatic cancer (mPC) treated with nab-paclitaxel in combination with gemcitabine. METHODS: In this open-label, single-arm, multicenter, phase II trial, patients received 4-week cycles of intravenous (i.v.) nab-paclitaxel at a dose of 125 mg/m2, followed by i.v. injections of gemcitabine at a dose of 1000 mg/m2 on days 1, 8 and 15 until disease progression or unacceptable toxicity was observed. The primary outcome was the HRQoL (deterioration-free rate at 3 months as evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. RESULTS: Eighty patients (median age: 74.6 years) were enrolled (56 with mPC, 24 with LAPC). The percentage of patients who had not experienced deterioration at 3 months was 54.3% (95% CI 41.6-67.0%). The median (interquartile range) time until definite deterioration was 1.6 (1.1-3.7) months. The objective response rate and clinical benefit rate were achieved by 11 (13.8%, 95% CI 6.2-21.3%) and 54 patients (67.5%, 95% CI 57.2-77.8%), respectively. The median overall survival was 9.2 months (95% CI 6.9-11.5), and the median progression-free survival was 7.2 months (95% CI 5.8-8.5). Only fatigue and neutropenia demonstrated a grade 3-4 toxicity incidence > 20%. CONCLUSIONS: Our study confirms the clinical benefit of the combination of nab-paclitaxel and gemcitabine in an elderly population with pancreatic cancer in terms of improved survival and clinical response. However, we were unable to confirm a benefit in terms of quality-of-life.

Do Clinical Trials Meet Current Care Needs? Views of Digestive Oncology Specialists in Galicia (Spain) Using the Delphi Method.

Background: In recent years, abundant scientific evidence has been generated based on clinical trials (CT) in the field of oncology. The general objective of this paper is to find out the extent to which decision making is based on knowledge of the most recent CT. Its specific objectives are to pinpoint difficulties with decision making based on the CT performed and find out the motivations patients and clinicians have when taking part in a CT. Methodology: Combined, prospective study, based on the Delphi method. A lack of correspondence between the people who take part in CT and patients who come for consultation has been identified. A need for training in analysing and interpreting CT has also been identified and a lack of trust in the results of CT financed by the pharmaceutical industry itself has been perceived. Conclusions: There is a difficulty in selecting oncological treatment due to the lack of correspondence between the patients included in the CT and patients seen in consultation. In this process, real world data studies may be highly useful, as they may provide this group with greater training in interpreting CT and their results.

Cetuximab given every 2 weeks plus irinotecan is an active and safe option for previously treated patients with metastatic colorectal cancer.

BACKGROUND: We gathered data from multiple institutions on the cetuximab regimen of patients with metastatic colorectal cancer. METHODS: 126 patients from 19 centers were included from July 2006 to July 2007 in this prospective non-controlled study. Irinotecan-refractory metastatic colorectal cancer patients with Karnofsky >or=70 received cetuximab 500 mg/m(2) every 2 weeks (q2w) in combination with irinotecan 180 mg/m(2) q2w until disease progression or unacceptable toxicity. The primary endpoint was the progression-free rate at 12 weeks. RESULTS: Median age was 65 years; 65.9% male; colon/rectum 64.3/34.1%; Karnofsky status or=90% in 45.3/54.7% of the patients. The progression-free rate was 42.7 (95% CI 32.8-52.6) and 22.4% (95% CI 14.2-30.7) at 12 and 24 weeks, respectively. The main grade 3 or 4 toxicities were: diarrhea 13.5% and acne-like rash 10.3%. No grade 3 or 4 infusional or allergic reactions were reported. CONCLUSIONS: The progression-free rates confirm that cetuximab q2w in combination with irinotecan is an option, and is as active and safe as the standard weekly regimen.

FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial.

PURPOSE: 5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab. PATIENTS AND METHODS: VISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.5 mL blood. Patients received bevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and 5-fluorouracil 3200 mg/m2) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 then 2400 mg/m2) by intravenous administration every 2 weeks. The primary outcome was progression-free survival (PFS). RESULTS: The intention-to-treat population comprised 349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOX-bevacizumab, n=177). Median PFS was 12.4 months (95% CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3 months (95% CI 8.5 to 10.7) with FOLFOX-bevacizumab (stratified HR, 0.64; 95% CI 0.49 to 0.82; p=0.0006). Grade≥3 adverse events were more common with FOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOX-bevacizumab (p=0.0178). Treatment-related deaths occurred in 8 (4.7%) and 6 (3.4%) patients, respectively. CONCLUSIONS: First-line FOLFOXIRI-bevacizumab significantly improved PFS compared with FOLFOX-bevacizumab in patients with metastatic colorectal cancer and ≥3 CTCs at baseline, which indicate a poor prognosis. CTC count may be a useful non-invasive biomarker to assist with the selection of patients for intensive first-line therapy.

First-line panitumumab plus capecitabine for the treatment of older patients with wild-type RAS metastatic colorectal cancer. The phase II, PANEL study.

BACKGROUND: Despite the high morbidity and mortality of metastatic colorectal cancer (mCRC) in older patients, they have been underrepresented in clinical trials and their optimal treatment is yet to be determined. This open-label phase II study evaluated the benefits of panitumumab and capecitabine as a first-line chemotherapy regimen in older patients with wild-type [WT] RAS mCRC. PATIENTS AND METHODS: Patients (≥70 years; ECOG≤2) received 3-week cycles of panitumumab (9 mg/kg on day 1) plus capecitabine (850 mg/m2 twice daily on days 1-14) until disease progression or unacceptable toxicity. Response was evaluated every 9 weeks according to RECIST_1.1. Outcome measures were: objective response rate (ORR), duration of response (DoR), time to response (TTR), progression (TTP) and treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Twenty-seven patients (11 women; median age: 78 years; ECOG: 0 [26%], 1 [67%], 2 [7%]) were evaluated. Median follow-up was 17.7 months. Confirmed ORR (95%CI) was 44.4% (25.7-63.2), with 25.9% of patients achieving at least stable disease. Median (95%CI) DoR was 8.7 (5.5-10.4) months, and median TTR was 2.2 (1.9-2.8) months. Median TTP was 9.6 (4.8-11.5) months, with a median TTF of 5.2 (2.8-7.2) months. The median PFS was 7.5 (4.4-10.4) months, and the median OS was 23.7 (7.4-27.5) months. Seventeen (63%) patients reported panitumumab and/or capecitabine-related adverse events grade 3-4, with skin toxicity (18.5%) being the most common. Two (7.4%) deaths were treatment-related. CONCLUSION: This study suggests that panitumumab plus capecitabine is a safe and effective regimen in older patients with WT RAS mCRC.

Efficacy and safety of FOLFIRI/aflibercept in second-line treatment of metastatic colorectal cancer in a real-world population: Prognostic and predictive markers.

PURPOSE: The phase III VELOUR trial demonstrated efficacy with combined FOLFIRI-aflibercept in patients with metastatic colorectal cancer previously treated with oxaliplatin with or without bevacizumab versus placebo. The effect of FOLFIRI-aflibercept in routine clinical practice was evaluated. METHODS/PATIENTS: Overall survival (OS), progression-free survival (PFS), response and safety were analysed for 78 patients treated with FOLFIRI-aflibercept at six GITuD institutions. Exploratory analyses of prognostic and predictive markers of efficacy were performed. RESULTS: Patients had good general status (PS 0-1 96.2%), tumours were mostly RAS-mutant (75.6%), synchronous (71.8%), and left-sided (71.8%). Prior therapy included bevacizumab (47.4%) and anti-EGFR agents (12.8%). PFS was longer for metachronous than synchronous tumours (11.0 vs 5.0 months, P = 0.028), and for left-colon tumours (7.0 vs 3.0 months, P = 0.044). RAS-mutant status, first-line treatment and primary tumour surgery did not impact PFS. The disease control rate was 70.5%. The most common grade 3/4 toxicities were neutropenia (15.3%), asthenia (10.3%), diarrhea and mucositis (6.4% each). Dysphonia was reported in 39.7% of patients, and grade 3 hypertension in 3.8%. Development of hypertension (any grade) was significantly associated with a reduced risk of progression by multivariate analysis (HR = 2.7; 95%CI 1.3-5.4; P = 0.001). CONCLUSIONS: Efficacy with FOLFIRI-aflibercept in a real-life population was in line with results from the pivotal trial and toxicity was manageable with treatment adaptation. Survival outcomes were not impacted by primary tumour location, RAS-mutant status, first-line treatment or primary tumour surgery. Hypertension may be a surrogate marker of efficacy in this patient population.

Neo-adjuvant treatment of infiltrating transitional-cell carcinoma of the bladder with paclitaxel and cisplatin: a phase II trial.

BACKGROUND: A phase II multicentric trial of paclitaxel and cisplatin was conducted in previously untreated patients, with locally advanced transitional-cell carcinoma (TCC) of the bladder, to assess its toxicity and efficiency in preserving the bladder. METHODS: Forty-four patients with locally advanced TCC of the bladder (seven with T3a, 27 with T3b, and eight with T4a) were treated with paclitaxel 175 mg/m(2) over 3 h, and cisplatin 75 mg/m(2) over 30 min, on the first day of each 21-day treatment cycle. Therapy was continued for three cycles. Patients were re-evaluated and scheduled for radiotheraphy or radical surgery depending on tumoral response. Tumoral response was measured by citology, computed tomographical scans, and deep randomized biopsies of the bladder. RESULTS: Thirty-two out of 42 patients (76%; 95% confidence interval 45-93%) showed a major response (22 complete, and 10 partial). Response times ranged from 18 to 54 months. Three patients with T4 bladder primary tumors experienced a pathological CR. At a median follow-up of three years, 20 patients remain free of disease (47.6%), six patients are alive with disease (14.3%), 12 patients died of disease (28.5%), and four others died of unrelated causes (9.5%). Hematological toxicity included anemia, thrombocytopenia, and neutropenia. No grade four febrile neutropenia was observed. Non-hematological toxicity included alopecia (93.2%), diarrhea (11.4%), vomiting (18.5%) mucosytis (4.6%), and neuropathy (4.6%). Drug omissions or dose delay for adverse events were only necessary in one patient (2.2%), and three patients (6.8%), respectively. CONCLUSIONS: Paclitaxel and cisplatin is an active and well-tolerated neo-adjuvant regimen for previously untreated patients with pure TCC of the bladder, achieving a vesical preservation rate of 52%.