Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

Table 1 Patient and tumor characteristics (n = 119)

	Median	Range
Age at diagnosis (yr)	61	33-84
Age at MMC/capecitabine onset (yr)	64	37-85
Previous treatment duration (yr)	2.03	0.2-9.3
	n	Valid %1
Male gender	68	57.1
Smoking history	33	30.6
Ethnicity
Jewish Ashkenazi	61	51.3
Other	58	48.7
Family history of cancer
Any	67	67.7
GI	32	32.3
Synchronous metastatic disease	82	68.9
Liver metastases	97	81.5
Tumor grade
Well-moderate	85	71.4
Poor	34	28.6
Tumor location
Right colon	29	24.4
Left colon	90	75.6
KRAS mutation	44	44.4
NRAS mutation	3	7.5
BRAF mutation	1	5.3
MSI-H/ MMRd	2	7.4
MMC/capecitabine line
3rd	50	42.0
4th	35	29.4
Subsequent	34	28.6
Previous drug exposure
Oxaliplatin	119	100.0
Irinotecan	118	99.2
5-FU	118	99.2
Capecitabine	14	11.8
Bevacizumab	109	91.6
Cetuximab/panitumumab	51	42.9
Regorafenib	14	11.8
TAS-102	7	5.9
ECOG PS
0-1	70	58.8
> 1	49	41.2

¹Data were missing on smoking (11 patients), family history (20), KRAS (20), NRAS (79), BRAF (100), and MSI/MMR (92).

N: Number; MMC: Mitomycin C; GI: Gastrointestinal; MSI: Microsatellite instability; MMRd: Mismatch repair deficient; ECOG PS: Eastern cooperative oncology group performance status; 5-FU: 5-fluorouracil.

Table 2 Treatment delivery and subsequent therapies

	Median	Range	n	%
MMC/capecitabine	2.0	0.5-9.0
Cycles administrated
Duration of treatment (mo)	2.8	0.5-20.0
Patients beginning Tx at full dosage
MMC
Capecitabine			114	95.8
			45	37.8
Dose reductions
MMC			3	2.5
Capecitabine			16	13.5
Any			19	16.0
Dose intensity (median)
MMC (mg/m²/wk)	1.17	0.6-1.6
Capecitabine (g/m²/wk)	9.33	4.6-11.9
Treatment delay (> 3 d)
Yes			22	18.5
No			97	81.5
Reason for discontinuation
Progression			108	90.8
Toxicity			6	5.0
Other/unknown			5	4.2
Subsequent therapies
Any			35	29.4
Oxaliplatin			12	10.1
Irinotecan			8	6.7
5-FU			18	15.1
Bevacizumab			3	2.5
Cetuximab/panitumumab			6	5.0
Regorafenib			5	4.2
TAS-102			5	4.2
Other/clinical trial			8	6.7
None			84	70.6

MMC: Mitomycin C; Tx: Treatment; 5-FU: 5-fluorouracil.

Table 3 Adverse events

	CTCAE grade ≥ 3		CTCAE grade 4
	n	%	n	%
Any	34	28.6	2	1.7
Hematological (n = 25)
Leukopenia
Neutropenia	4	3.4	1	0.8
Thrombocytopenia	3	2.5	1	0.8
Anemia	6	5.0	1	0.8
	12	10.1	0	0
Non-hematological (n = 29)
Bleeding
Diarrhea	4	3.4	0	0
Nausea	9	7.6	1	0.8
Vomiting	3	2.5	0	0
Stomatitis	6	5.0	0	0
Dermal	2	1.7	0	0
HFS	1	0.8	0	0
	4	3.4	0	0

CTCAE: Common terminology criteria for adverse events; HFS: Hand-foot syndrome; SAEs: Serious adverse events.

Table 4 Previous studies of mitomycin C/capecitabine as advanced line therapy in metastatic colorectal cancer

Ref.	Phase	Line of treatment	Number of patients (evaluable)	Study period (mo/yr)	Grade ≥ 3 AEs (%)	ORR (%)	DCR (%)	Median PFS (mo)	Median OS (mo)	1-yr OS (%)
Prospective studies
Chong et al[2], 2005	II	3	36 (33)	07/2001- 11/2003	NR1	15.2	63.7	5.4	9.3	30.6
Lim et al[19], 2005	II	3	21 (19)	03/2003- 03/2004	NR1	4.8	26.3	2.6	6.8	NR
Scartozzi et al[17], 2006	II	3	61	NR	NR1	8.0	48.0	3.0	6.0	NR
Retrospective studies
Chua et al[23], 2008	-	3	18 (14)	06/2003- 06/2007	16.7	0	11.0	2.7	5.4	NR
Saif et al22], 2013	-	4	15	07/2007- 02/2013	0	20.0	53.0	NA	NA	NR
Martorana et al[21], 2017	-	3	61	01/2008- 12/2014	9.0	5.0	29.5	3.3	9.3	NR
Current, 2023	-	≥ 3	119	03/2006- 11/2020	28.6	0.8	24.4	2.1	4.2	15.8

¹Studies reported the rates of each AE individually and did not report the total proportion of patients who experienced adverse events.

MMC: Mitomycin C; mCRC: Metastatic colorectal cancer; AE: Adverse event; ORR: Objective response rate; DCR: Disease control rate; PFS: Progression free survival; OS: Overall survival; NR: Not reported; NA: Not available.