Phase I trial of capecitabine (Cap) and gemcitabine (G) with concurrent radical radiotherapy in locally advanced pancreatic ca..

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2006 Gastrointestinal Cancers Symposium
Abstract No:125

M. Michael, T. Leong, T. Price, V. Ganju, A. Strickland, M. Jefford ,
A. Muller, S. Ngan, A. Milner, J. R. Zalcberg
Primary chemoradiation with infusional 5FU is widely used for the
treatment of patients (pts) with locally advanced, unresectable PaC,
but with disappointing results. To improve efficacy and pt convenience
novel chemotherapy regimens need to be evaluated in combination with
radical radiotherapy (RT). The combination of Cap and G has shown
activity in advanced PaC and both agents are potent radiosensitisers.
The aim of this phase I trial was to determine the MTD of the Cap plus
G combination with concurrent RT in pts with localised PaC.
Eligible pts had unresectable, locally advanced PaC based on imaging
and/or surgical staging, adequate organ function, ECOG PS 0-1 and no
prior therapy. During RT, G was escalated from 20 to 50 mg/m2/day IV (given days 1 and 4 of each week of RT), and Cap was escalated from 800 to 2,000 mg/m2/day
(given daily in 2 divided doses, days 1-5 of each week of RT) in 7
planned dose levels. RT consisted of 50.4 Gy/28 fractions/5.5 weeks
using conformal techniques. Three pts were entered to each dose level
and if 1 of 3 pts had a dose limiting toxicity(s) (DLTs) the cohort was
expanded to 6 pts. DLTs were defined prospectively and based on
treatment related toxicities and treatment interruptions.
Results: 16 pts have been accrued to date, with complete data on 11. Dose level 1: Cap/G; 800 mg/m2/day/20 mg/m2/day
(3 pts). Dose level 2: 1,000/20 (7 pts). Dose level 3: 1,300/30 (6
pts). Three pts (27%) had a PR, and 6 pts (55%) had SD. No DLTs were
observed on dose levels 1 and 2, whilst 2 DLTs were observed in dose
level 3; grade 3 dehydration (1 pt) and grade 3 diarrhoea and
dehydration (1 pt). Dose level 2 was declared the recommended dose
level and is being expanded to a total of 12 pts. No grade 4
haematological toxicities have been observed.
Conclusions: The addition of Cap and G to radical RT was both feasible and generally well tolerated. For future trials, Cap 1,000 mg/m2/day and G 20 mg/m2/day (twice per week) is the recommended dose when combined with 50.4Gy of RT. Updated results will be presented.