Cetuximab in combination with capecitabine, irinotecan, and radiotherapy for patients with locally advanced rectal cancer: results of a Phase II MARGIT trial.
OBJECTIVE
To evaluate the safety and efficacy of preoperative radiotherapy (RT) in combination with cetuximab, capecitabine, and irinotecan in patients with locally advanced rectal cancer.


METHODS
Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive cetuximab (400 mg/m(2) Day 1, 250 mg/m(2) Days 8, 15, 22, 29) in combination with weekly irinotecan 40 mg/m(2) and capecitabine 500 mg/m(2) twice daily (Days 1-38). RT was given to a dose of 50.4 Gy (45 + 5.4 Gy). Primary endpoint was toxicity, and antitumor activity as assessed by the pathologic complete remission (pCR) rate was a secondary endpoint.


RESULTS
Fifty patients were enrolled; 88% showed T3 or T4 and 76% nodal-positive tumors with a median distance from the anal verge of 7.5 cm. The actual dose intensity was as follows (median/mean, %): cetuximab 100/92, irinotecan 100/91, capecitabine 100/89). Main adverse events Grades 2/3/4 were (National Cancer Institute common toxicity criteria version 3.0, %): leukocytopenia 6/2/2, nausea/vomiting 4/2/0, diarrhea 34/30/0, proctitis 26/2/0, elevation of liver transaminases 8/10/0, and acnelike skin rash 46/6/0. All patients underwent surgery, and no postoperative deaths occurred. Eighty-four percent underwent low-anterior resection, and 68% of the specimen exhibited moderate or good tumor regression, but only 4 patients had a pCR.


CONCLUSIONS
Preoperative chemoradiation with cetuximab-CapIri-RT has manageable toxicity, with diarrhea being the most commonly observed adverse event. Nevertheless, the efficacy of this regimen with a pCR rate of only 8% was significantly lower than that observed in a previous Phase I trial.
Horisberger
Karoline
K
Chirurgische Klinik und Poliklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Germany.
Treschl
Anne
A
Mai
Sabine
S
Barreto-Miranda
Manuel
M
Kienle
Peter
P
Ströbel
Philipp
P
Erben
Philipp
P
Woernle
Christoph
C
Dinter
Dietmar
D
Kähler
Georg
G
Hochhaus
Andreas
A
Post
Stefan
S
Willeke
Frank
F
Wenz
Frederik
F
Hofheinz
Ralf-Dieter
RD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D000068818:Cetuximab; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D007970:Leukopenia / Q000209:etiology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D011349:Proctitis / Q000209:etiology; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012074:Remission Induction; D014839:Vomiting / Q000209:etiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin