Neoadjuvant chemotherapy in locally advanced colon cancer. A phase II trial.
BACKGROUND
Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan.


METHODS
Patients with resectable colon cancer fulfilling the following criteria were offered inclusion; Histopathological verification of adenocarcinoma, T3 tumor on CT scan with extramural tumor invasion > 5 mm or T4 tumor, age ≥ 18 years, PS ≤ 2, adequate hematology, and informed consent. Patients with KRAS, BRAF or PIK3CA mutation or unknown mutational status received three cycles of capecitabine 2000 mg/m(2) days 1-14 q3w and oxaliplatin 130 mg iv day 1 q3w. Wild-type patients received the same chemotherapy supplemented with panitumumab 9 mg/kg iv q3w. After the operation, patients fulfilling the international criteria for adjuvant chemotherapy, i.e. high-risk stage II and III patients, received five cycles of the same chemotherapy without panitumumab. Patients not fulfilling the criteria were offered follow-up only. The primary endpoint was the fraction of patients not fulfilling the criteria for adjuvant chemotherapy (converted patients). Secondary endpoints were recurrence rate, disease-free survival (DFS), and toxicity.


RESULTS
The study included 77 patients. The conversion rate was 42% in the wild-type group compared to 51% in patients with a mutation. The cumulative recurrence rate in converted versus unconverted patients was 6% versus 32% (p = 0.005) translating into a three-year DFS of 94% versus 63% (p = 0.005).


CONCLUSIONS
Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. Validation in a randomized trial is warranted.
a Department of Oncology , Vejle Hospital , Vejle , Denmark.|i Institute for Regional Health Research, University of Southern Denmark , Odense , Denmark.
Anders
A
Jakobsen
e Department of Oncology , Hillerød Hospital , Hillerød , Denmark.
Fahimeh
F
Andersen
h Department of Surgical Gastroenterology , Herlev Hospital , Herlev , Denmark.
Anders
A
Fischer
a Department of Oncology , Vejle Hospital , Vejle , Denmark.
Lars H
LH
Jensen
d Department of Surgery , Vejle Hospital , Vejle , Denmark.
Jens C R
JC
Jørgensen
g Department of Oncology , Herlev Hospital , Herlev , Denmark.
Ole
O
Larsen
b Department of Pathology , Vejle Hospital , Vejle , Denmark.
Jan
J
Lindebjerg
a Department of Oncology , Vejle Hospital , Vejle , Denmark.
John
J
Pløen
c Department of Radiology , Vejle Hospital , Vejle , Denmark.|i Institute for Regional Health Research, University of Southern Denmark , Odense , Denmark.
Søren R
SR
Rafaelsen
f Department of Surgery , Hillerød Hospital , Hillerød , Denmark.
Jesper
J
Vilandt
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D058534:Class I Phosphatidylinositol 3-Kinases; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011859:Radiography; D015996:Survival Rate; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D000077544:Panitumumab; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)