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

Figures & data

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.

Table 1 Patient characteristics (N=86)

Characteristics	Number	%
Sex
Male	49	57.0
Female	37	43.0
Median age, years (range)	65 (36–81)
ECOG PS
0	81	94.2
1	5	5.8
Location of tumor
Colon	54	62.8
Rectum	32	37.2
Histological outcome
Well	14	16.3
Moderate	65	75.6
Poor	5	5.8
Others	2	2.3
Disease stage
II	15	17.4
IIIa	47	54.7
IIIb	24	27.9

Abbreviation: ECOG PS, Eastern Cooperative Oncology Group performance status.

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.

Table 2 Proportion of patients completing treatment and dose of oxaliplatin in the treatments

	All patients	mFOLFOX6	CAPOX	P-value
Number	86	30	56
Proportion of completion (%)
Oxaliplatin based therapy	83.7	80.0	85.7	0.544
All treatments	65.1	63.3	66.1	0.816
Median dose of oxaliplatin (range) mg/m^2	479 (82–531)	467 (82–512)	490 (120–531)	0.123

Abbreviations: FOLFOX, folinic acid, fluorouracil, and oxaliplatin; mFOLFOX6, modified FOLFOX; CAPOX, capecitabine and oxaliplatin.

Table 3 Adverse events

	All patients, %		mFOLFOX6 (n=30), %		CAPOX (n=56), %		P-value (Fisher test: all grades)
	All	≥ Grade 3	All	≥ Grade 3	All	≥ Grade 3
Leukopenia	34.9	0	33.3	0	35.7	0	1
Neutropenia	57	9.3	53.3	3.3	58.9	12.5	0.653
Anemia	53.5	0	70	0	44.6	0	0.04
Thrombocytopenia	62.8	2.3	60	3.3	64.3	1.8	0.816
T-Bil	9.3	0	6.7	0	10.7	0	0.708
AST	67.4	0	73.3	0	64.3	0	0.473
ALT	47.7	5.8	56.7	6.7	42.9	5.4	0.262
ALP	25.6	1.2	16.7	0	30.4	1.8	0.202
Cre	8.1	1.2	13.3	3.3	5.4	0	0.232
HFS	50	3.5	63.3	3.3	42.9	3.6	0.113
Anorexia	47.7	4.7	56.7	0	42.9	7.1	0.262
Diarrhea	26.7	8.1	23.3	10	28.6	7.1	0.799
Nausea	30.2	1.2	26.7	0	32.1	1.8	0.632
Oral mucositis	25.6	1.2	46.7	3.3	14.3	0	0.001
PSN	81.4	3.5	86.7	3.3	78.6	3.6	0.402
PMN	22.1	1.2	16.7	0	25	1.8	0.427

Abbreviations: FOLFOX, folinic acid, fluorouracil, and oxaliplatin; mFOLFOX6, modified FOLFOX; CAPOX, capecitabine and oxaliplatin; PSN, peripheral sensory neuropathy; PMN, peripheral motor neuropathy; AST, aspartate transaminase, ALT, alanine transaminase, ALP, alkaline phosphatase, Cre, creatinine, HFS, Hand-Foot Syndrome.

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.

Table 4 Correlation between PNQ and CTCAE by Spearman’s correlation coefficient

	CTCAE-motor		r	P-value
	0 and 1	≤2
PNQ-motor
A, B	257	2	0.127	0.038
≥ C	11	0
PNQ-sensory
A, B	221	8	0.468	<0.01
≥ C	32	6

Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events version 4.0; 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.