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Irinotecan plus Oxaliplatin versus Irinotecan plus 5-FU/Folinic Acid as First-Line Treatment
in Metastatic Colorectal Cancer: Interim Toxicity Analysis of a Randomized Phase III Trial.
A. Schalhorn1, M. Stauch2, D. Quietzsch3, P. A. Maubach4, L. Fischer von Weikersthal5, G. Schlimok6, U. Bruntsch7, H. Lambertz8, M. Grundeis9, M. Schulze10, J. Stamp, W. Hiddemann1, and V. Heinemann1
1Medical Dept. III, University of Munich, 2Oncologic Practice, Kronach, 3Dept. of Oncology, Clinic Chemnitz, 4Oncologic Practice, Ingolstadt, 5Medical Dept. II, Clinic St. Marien Amberg, 6Medical Dept. II, Clinic Augsburg,
7Medical Dept.V, Clinic Nuernberg Nord, 8Dept. of Oncology, Clinic Garmisch, 9Oncologic Practice, Chemnitz, 10Dept. of Oncology, Clinic Zittau
Abstract: 594
Purpose: This phase III multicenter trial was designed to compare the • Primary endpoint:
Inclusion criteria
efficacy and toxicity of a first-line treatment with 5-FU/FA plus irinotecan Medizinische Universitätsklinik Würzburg (arm A) to the combination of irinotecan plus oxaliplatin (arm B) in • Secondary endpoints:
z histologically proven adenocarcinoma of colon or rectum metastatic CRC. Patients and Methods: Between July 2000 and Privatklinik Dr. R. Schindlbeck Herrsching Fischer von Weikersthal Klinikum St. Marien Amberg Campto + AIO
Campto + Oxaliplatin
November 2001, 159 pts from 36 centres were enrolled. Patients (pts) z bidimensionally measurable lesions (CT/MRT >20mm, chest X-ray were randomised to receive either irinotecan 80mg/m2 plus FA 500mg/m2 plus 5-FU 2000 mg/m2 (24h) given weekly for 6 times (arm A) or oxaliplatin 85mg/m2 (d1, 15, 29) followed by irinotecan 80mg/m2 weekly z no previous chemotherapy for metastatic disease times 6 (arm B). Cycles were repeated on day 50 in both arms. A cross- over design allowed to switch over progressing pts to the respective Campto + Oxaliplatin Campto + AIO
z clinical evaluation < 3 weeks before randomisation comparator regimen. Results: To date, toxicity data are evaluable in 42 pts receiving arm A (median age: 65 yrs; male/female: 29/13) in 69 cycles Stratification:
Exclusion criteria
and in 46 pts treated in arm B (median age: 63 yrs; male/female 30/16) in z Performance Status: Karnofsky Index: 100% vs 70-90%
96 cycles. Dose reductions (<80% of planned dose) were observed for 5- FU in 29% (arm A), irinotecan in 14%/16% (arm A/B), and for oxaliplatin in O LDH: < 240 U/L versus >240 U/L
34% of cycles (arm B). Conclusion: Toxicity was acceptable in both O Adjuvant pretreatment:
treatment arms and no signficant difference was observed in the planned O clinically symptomatic peritoneal carcinosis (ascites) CPT 80 mg/m2 0.5h, day 1, 8, 15, 22, 29, 36, sample size:
Irinotecan plus FU/FA
Irinotecan plus Oxaliplatin
Safety Parameter
O chronic inflammatory GI disease / ileus based on TTP improvement from 6.7 months to 8.5 months (25%)
O clinical y symptomatic brain metastasis Hematological Toxicity (per cycle analysis) Parameter
Total (%) Arm A (%) Arm B (%)
NCI-CTC Grade 3-4 Toxicity
median(range) median(range)
median(range)
Adjuvant Pretreatment
(CPT/FuFA)
(CPT/Ox)
Total (%)
Age (years)
62 (28-76)
63 (32-83)
62 (28-76)
(CPT/FuFA)
(CPT/Ox)
Atropine
Gender (m/f)
LDH <240 U/l
Leucocytopenia
Loperamide
Dose reduction
Colon cancer
LDH >240 U/l
CPT-11 + FU/FA
CPT-11 + Oxaliplatin
Rectal cancer
Thrombocytopenia
Budesonide
NCI-CTC Grade
Performance status 100%
Cycles delayed
Leucocytes
Octreotide
Performance status
Neutropenic Fever
Previous
Thrombocytes
radiotherapy
HT3-antagonists
Non-Hematological Toxicity (per cycle analysis) Neutropenic Fever
• Toxicity was acceptable in both treatment arms.
NCI-CTC Grade 3-4 Toxicity
Vomiting
• Hematotoxicity (grade 3-4) was low and generally (CPT/FuFA)
(CPT/Ox)
Diarrhea early
Arm A (%) Arm B (%)
Diarrhea delayed
23.5 30.9 7.4
(CPT/FuFA)
(CPT/Ox)
• Non-hematological toxicity (grade 3-4) occurred in Total (%)
Arm A (%) Arm B (%)
Constipation
Complete remission
<6% of cycles (apart from delayed diarrhea).
(CPT/FuFA)
(CPT/Ox)
5-FU / FA Bolus
Cholinergic Synd.
Alopecia
Progression of disease
Patients recuited
5-FU / FA High-dose (AIO)
• Delayed diarrhea (grade 3-4) was significantly Patients evaluable for
Radiochemotherapy
more frequent (19.4% vs 6.7%, p=0.0005) in Mucositis
toxicity
patients receiving the CPT-11/oxaliplatin Toxicity
Cycles evaluable for toxicity
Immune therapy
Neurological
Compliance
• Doses were reduced in 25% of cycles and were

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