Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study

Abstract

Background: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine.

Patients and methods: Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m² on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire.

Results: Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47).

Conclusion: A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.

Keywords: Patient Neurotoxicity Questionnaire; adjuvant chemotherapy; oxaliplatin; peripheral neurotoxicity.

Figure 1

Study design (JSWOG-C2). Abbreviations: CAPOX, capecitabine and oxaliplatin; CTCAE, Common Terminology Criteria for Adverse Events version 4.0; FOLFOX, folinic acid, fluorouracil, and oxaliplatin; LV, leucovorin; M, months; mFOLFOX6, modified FOLFOX; OX, Oxaliplatin; PNQ, Patient Neurotoxicity Questionnaire; q2w, every 2 weeks; JSWOG, Japan Southwest Oncology Group; L, optical isomer.

Figure 2

PNQ – oxaliplatin. Abbreviation: PNQ, Patient Neurotoxicity Questionnaire.

Figure 3

CONSORT diagram for this study. Notes: In total, 91 patients from eleven hospitals were enrolled. Two patients were excluded for not fulfilling the eligibility criteria, and three were excluded for refusing to continue treatment. Abbreviation: CONSORT, consolidated standards of reporting trials.

Figure 4

Frequency of neurotoxicity at four points: baseline and months 1.5, 3, and 6 after induction of adjuvant chemotherapy. Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events version 4.0; M, months; PNQ, Patient Neurotoxicity Questionnaire.

Figure 5

PSN during oxaliplatin treatment and at month 6. Abbreviation: PSN, peripheral sensory neuropathy.

Figure 6

Changes in PNQ and CTCAE between PSN+ and PSN− groups at month 6. Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events version 4.0; M, months; PNQ, Patient Neurotoxicity Questionnaire; PSN, peripheral sensory neuropathy; ns, not significant.

Figure 7

DFS. Abbreviations: DFS, disease-free survival; CAPOX, capecitabine and oxaliplatin; FOLFOX, folinic acid, fluorouracil, and oxaliplatin.