A prospective Phase II study to examine the relationship between quality of life and adverse events of first‐line chemotherapy plus cetuximab in patients with KRAS wild‐type unresectable metastatic colorectal cancer: QUACK trial

Abstract

A prospective trial has not been performed to investigate associations between quality of life (QOL), adverse events (AEs), and overall survival (OS) in the first‐line treatment with cetuximab plus standard chemotherapy for advanced/metastatic colorectal cancer (mCRC). Associations between patient outcome and health‐related QOL (HRQOL) together with skin toxicity‐related QOL were prospectively evaluated using EORTC QLQ‐C30 and DLQI questionnaires. One hundred and forty mCRC patients were analyzed in this study, and 87.8% received pre‐emptive skin treatment. Skin toxicity had no clinical impact on HRQOL or skin‐related QOL during the first 8 weeks and throughout the study period. An early skin reaction with a grade ≥2 at 8 weeks was significantly associated with a favorable OS compared with a grade of ≤1 (HR, 0.50; 95% CI, 0.24‐0.95; P = .035) and was confirmed to be an independent predictor of OS (HR, 0.48; 95% CI, 0.21‐0.97; P = .040). Patients symptomatic at baseline who responded to treatment had improved HRQOL compared to nonresponding patients. Severe mucositis/stomatitis had a statistically significant and clinically meaningful negative impact on HRQOL (mean changes from baseline throughout the study period in global health status were −12.64 for a grade of ≥2 vs −0.35 for a grade of 0 or 1 (P = .005)). In conclusion, severe early skin reactions predict favorable OS for patients treated with cetuximab plus chemotherapy without impairing QOL. In addition, mucositis/stomatitis was the most substantial AE compromising both QOL and treatment compliance.

Patient‐reported symptom burden as a prognostic factor in treatment with first‐line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial

“…As described previously, the safety profile in this study was consistent with the results of prior clinical trials . No significant differences in the overall incidence of grade 3 or higher AEs were observed between the patients with and without symptoms (40% vs 50%; P = .295), and both categories of patients also showed similar AE profiles with a grade of ≧ 2 (Table ).…”

“…In some instances, specific symptoms were likely to have prognostic value: for example, dysphagia in esophageal cancer, loss of appetite in breast cancer and in CRC, and pain in lung cancer and in CRC . In addition, mucositis/stomatitis was the most substantial AE compromising both QOL and treatment compliance in CRC, as reported previously . However, it is unclear which symptoms had the greatest impact on OS outcomes when treatment used cetuximab plus chemotherapy due to the small sample size.…”

“…One hundred and forty‐nine mCRC patients were enrolled from 49 institutions between July 2013 and April 2015 (Table ). Nine patients were terminated from the study before the first administration of the study treatment, and 140 patients received the first‐line cetuximab plus chemotherapy . The FOLFIRI plus cetuximab regimen consisted of an initial infusion of 400 mg/m 2 of cetuximab, followed by a weekly infusion of 250 mg/m 2 , with the concurrent administration of 200 mg/m 2 of l‐leucovorin and 150 mg/m 2 irinotecan; this was followed by an intravenous bolus of 400 mg/m 2 of 5‐fluorouracil, with a continuous infusion of 2400 mg/m 2 for 46 hours every 14 days.…”

Hand Foot Syndrome Has the Strongest Impact on QOL in Skin Toxicities of Chemotherapy

“…There have been some reports that focused on the worst grade skin disorder and decreased quality of life [10-14, 18, 19]. Some reports have found negative impact on QOL [10][11][12] and the others have not [13,14,18,19]. In our study, negative impact was obtained.…”

“…Chemotherapy sometimes causes side effects of skin disorders such as hand foot syndrome, rash, paronychia, xerosis and pigmentation [1][2][3][4][5][6]. Not only do those skin disorders make it difficult to continue treatment, they can also cause impairment of the patient's quality of life [10][11][12][13][14][15][16][17][18][19]. Therefore, when using anticancer drugs with skin toxicity, prevention, early detection and treatment of skin disorders are essential [11,13,20,21].…”