title: Early tumor shrinkage in metastatic colorectal cancer: retrospective analysis from an irinotecan-based randomized first-line trial.
abstract: Early tumor shrinkage (ETS) has been highlighted as a favorable prognostic factor related to progression-free survival (PFS) and overall survival (OS) in cytotoxic treatment of metastatic colorectal cancer. Data from a randomized phase III study comparing infusional 5-fluorouracil plus irinotecan (FUFIRI) versus irinotecan plus oxaliplatin (mIROX) were evaluated. Patient groups were analyzed according to the relative change in maximum tumor diameter between baseline and after 7 weeks of treatment. The ETS cohort was defined as a decrease of ≥20%. Additionally, the non-ETS cohort was subdivided into "minor shrinkage" (0-19%), "tumor progression" (any increase) and development of "new metastatic lesions". Progression-free survival and OS were estimated in all patient subgroups. Assessment of ETS was possible in 201 patients. Early tumor shrinkage was observed in 47% (94/201) and non-ETS in 53% (107/201) of patients. Patients with ETS had a more favorable outcome with regard to PFS (9.9 months vs 6.1 months, P = 0.029) and OS (27.5 months vs 17.8 months, P = 0.002). In the non-ETS subgroups, patients with "minor shrinkage" (PFS 8.4 months, OS 21.6 months) showed a markedly better outcome than patients with "early tumor progression" (PFS 4.0 months, OS 15.3 months) or with "new metastatic lesions (PFS 2.2 months, OS 7.6 months). In conclusion, ETS assessment offers accelerated response evaluation when compared to RECIST. In patients treated with chemotherapy alone, ETS ≥20% is associated with excellent outcome. Non-ETS is a heterogeneous subgroup where patients with minor shrinkage clearly benefit from treatment, and patients with early progression or development of new lesions have an unfavorable prognosis.
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, Ludwig-Maximilians-University of Munich, Munich, Germany. clemens.giessen@med.uni-muenchen.de
authors.forename: Clemens
authors.initials: C
authors.lastname: Giessen
authors.forename: Ruediger P
authors.initials: RP
authors.lastname: Laubender
authors.forename: Ludwig
authors.initials: L
authors.lastname: Fischer von Weikersthal
authors.forename: Andreas
authors.initials: A
authors.lastname: Schalhorn
authors.forename: Dominik P
authors.initials: DP
authors.lastname: Modest
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stintzing
authors.forename: Michael
authors.initials: M
authors.lastname: Haas
authors.forename: Ulrich R
authors.initials: UR
authors.lastname: Mansmann
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin