A Phase I–II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

Figures & data

Table I. Dose levels in Phase I Part.

Dose level	Gemcitabin 10 mg/m^2/min mg/m^2 days 1 and 14	Capecitabine p.o. BID mg/m^2 days 1–7 and 14–21	Oxaliplatin mg/m^2 days 1 and 14
Level 1	800	1 000	60
Level 2	1 000	1 000	60
Level 3	1 000	1 250	60
Level 4	1 000	1 250	85
Level 5	1 200	1 250	85
Level 3A	1 000	1 000	85

Dose level 3A was introduced after protocol amendment.

Table II. Demographics of the patients in the Phase II part.

Median age	61	(35–75)
Gender (M/F)	16/25	39%/61%
Performance status:
0	16	39%
1	19	46%
2	6	15%
Diagnosis:
Intrahepatic	8	20%
Ductus hepaticis dxt	7	17%
Ductus hepaticus sin	5	12%
Klatskin tumor	10	24%
Gall Bladder	5	12%
Ductus choledochus	4	10%
Unknown	2	5%
Site:
Vejle Hospital	11	27%
Rigshospitalet	30	73%

Table III. Adverse events, Phase II part, by Common Toxicity Criteria version 3.0.

N = 41 patients	Grade 1 (%)	Grade 2 (%)	Grade 3 (%)	Grade 4 (%)
Nausea	19 (46)	8 (20)	1 (2)	–
Vomiting	5 (12)	3 (7)	1 (2)	–
Diarrhea	17 (42)	10 (5)	1 (<1)	–
Fatigue	15 (37)	20 (49)	1 (2)	–
PPE	2 (5)	3 (7)	–	1 (2)
Neuropathy	20 (49)	8 (20)	4 (10)	–
Thrombo-embolic event	–	–	2 (5)	2 (5)
Infection	4 (10)	1 (2)	6 (15)	–
Neutropenia	2 (5)	6 (15)	11 (27)	12 (29)
Thrombocytopenia	15 (37)	6 (15)	2 (5)	3 (7)

PPE: palmo-plantar erythodysaestesia.

Table IV. Response rates, Phase II part (intention-to-treat).

N = 41	Frequency	Percent
Complete remission	3	7
Partial remission	11	27
Stable disease	21	51
Progressive disease	3	7
Not evaluable	3	7
	Months	Range
Median suvival	12.5 (95% CI 9.2–15.9)	0.39–23.7 months
Median PFS	6.9 (95% CI 5.1–8.6)	0.16–23.9 months

Overall response rate was 34% and clinical benefit rate (CR + PR+SD) was 85%.

PFS: progression-free survival.

Figure 1. Kaplan-Meier plot of overall survival and progression-free survival (PFS) of 41 patients treated in the Phase II part of the study. Median survival was 12.5 months (95% CI 9.2–15.9) and median PFS was 6.9 months (95% CI 5.1–8.6).