Mean (SE) baseline scores for responding patients progressing patients with WT tumours were 0

Mean (SE) baseline scores for responding patients progressing patients with WT tumours were 0.81 (0.03) 0.72 (0.18), respectively; mean scores in responding progressing patients with MT tumours were 0.82 (0.05) 0.59 (0.20). skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 0.78), health rating scores (72.5 71.0) and QLQ-C30 global health status scores (65.8 66.7) were comparable at baseline safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity. Conclusions First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity. Trial registration ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT00508404″,”term_id”:”NCT00508404″NCT00508404 Rabbit Polyclonal to CtBP1 tumours [3,4]. As median overall survival (OS) in patients with metastatic colorectal cancer now approaches 2 years [5], long-term tolerability of treatment is usually important. Although patients have undoubtedly benefitted from the integration of novel brokers, the use of combination regimens inevitably leads to greater treatment-related toxicity [6] and potentially, adverse effects on quality of life. While FOLFIRI is usually associated AZD4547 with severe diarrhoea and neutropenia [7], EGFR inhibitors are associated with unique side effects, mostly different to those seen during chemotherapy. Because of the key role of EGFR signalling in skin [8], anti-EGFR therapy frequently results in integument-related toxicities [9]. Acneiform rash is the most common but xerosis, paronychia and trichomegaly also occur [10]. Although dermatological toxicities often resolve upon therapy discontinuation [11], these side effects can negatively affect treatment compliance and quality of life [12]. They can also lead to dose modification or discontinuation [13], thus potentially affecting the overall effectiveness of anti-EGFR treatment. Maintenance of quality of life is therefore an important treatment goal and patient-reported outcomes (PROs) are a useful way of measuring the impact of treatment on quality of life. Study 314 (“type”:”clinical-trial”,”attrs”:”text”:”NCT00508404″,”term_id”:”NCT00508404″NCT00508404) was a single-arm, multicentre, phase II study evaluating the efficacy and safety of panitumumab plus FOLFIRI as first-line treatment for patients with metastatic colorectal cancer. In this study, consistently favourable efficacy was observed in patients with WT mutant (MT) tumours [14]. Here we report additional descriptive tolerability and quality of life data from Study 314. Methods Study design and treatments At the time of study initiation, the value of tumour status in patients receiving anti-EGFR therapies was unknown but after its importance was exhibited [15,16] the protocol was amended to evaluate outcomes by status (the study was fully enrolled at this time). Panitumumab and FOLFIRI were administered once every 14 days until disease progression, unacceptable toxicity, or consent withdrawal. If FOLFIRI or panitumumab were withdrawn/withheld due to toxicity, the other agent could be continued. On Day 1 of the first cycle, panitumumab (6 mg/kg) was administered as a 60??15 min intravenous (IV) infusion, just prior to chemotherapy; if well tolerated, subsequent infusions could be administered over 30??10 min. No panitumumab-specific premedication was required. FOLFIRI AZD4547 (irinotecan [180 mg/m2 IV over 90??15 min and leucovorin [400 mg/m2 IV over 120??15 min [given sequentially/in parallel], followed by a 5-FU 400 mg/m2 bolus and a 5-FU 2400C3000 mg/m2 continuous IV infusion over 46??2 h) was also administered on Day 1 of each cycle. One cycle was defined as the 14-day period following treatment initiation. The study protocol was approved by the relevant impartial ethics committees and the study was conducted in accordance with International Conference on Harmonization of Good Clinical Practice AZD4547 regulations/guidelines. Patients Eligible patients were 18 years of age, with histologically/cytologically confirmed, radiologically measurable metastatic colorectal cancer, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0C2. All disease sites must have AZD4547 been evaluated 28 days prior to enrolment and tissue.