Oxaliplatin and capecitabine-based chemoradiotherapy for gastric cancer--an extended phase I MARGIT and AIO trial.
OBJECTIVE
Adjuvant 5-fluorouracil-based chemoradiotherapy has been shown to improve the prognosis of gastric cancer. To optimize these results, in the present study oxaliplatin and capecitabine were used instead of 5-fluorouracil. We sought to determine the maximum tolerated dose and the dose-limiting toxicities (DLT) of these drugs in combination with intensity-modulated radiotherapy.


METHODS
Patients with resected adenocarcinoma of the stomach or the gastroesophageal junction were included. They received two cycles of induction chemotherapy (oxaliplatin and capecitabine [XelOx] regimen). Using standard Phase I methodology, patients received 45 Gy in 1.8-Gy fractions either in combination with capecitabine 825 mg m(-1) twice a day (Dose Level [DL] I) or capecitabine in combination with weekly oxaliplatin 40 or 50 mg m(-1) (DL II and III). After the completion of chemoradiation, two additional cycles of XelOx were scheduled.


RESULTS
A total of 32 patients were recruited. Only 1 of 6 patients evaluable on DL I had DLT. Of the first 6 patients on DL II, 1 patient experienced DLT, and 3 of the remaining patients had Grade 3 toxicity. Therefore, DL II was defined as the maximum tolerated dose and a total of 20 patients were treated at this DL. The most frequently observed toxicities (Common Toxicity Criteria Grades 1, 2 and 3) were, respectively, leukocytopenia in 5, 5, and 4 patients; nausea in 3, 7, and 3; and diarrhea in 4, 0, and 1.


CONCLUSIONS
In summary, capecitabine 825 mg m(-1) twice a day (Days 1-33) and weekly oxaliplatin 40 mg m(-1) was safe and tolerable in combination with intensity-modulated radiotherapy. Furthermore, four cycles of XelOx could be applied before and after chemoradiotherapy in two thirds of the patients.
Onkologisches Zentrum, III. Medizinische Klinik Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Heidelberg, Germany.
Ralf-Dieter
RD
Hofheinz
Frederik
F
Wenz
Nadine
N
Lukan
Sabine
S
Mai
Melanie
M
Kripp
Wilko
W
Staiger
Matthias
M
Schwarzbach
Frank
F
Willeke
Markus
M
Möhler
Stefan
S
Post
Andreas
A
Hochhaus
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D018714:Radiotherapy, Adjuvant / Q000379:methods*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy*
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil