ABSTRACT
The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Frontotemporal Dementia , Rectal Neoplasms , Humans , Quality of Life , Uracil/adverse effects , Colorectal Neoplasms/pathology , Prospective Studies , Trifluridine/adverse effects , Frontotemporal Dementia/chemically induced , Frontotemporal Dementia/drug therapy , Pyrrolidines/adverse effects , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Drug Combinations , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
PURPOSE: To determine whether irinotecan plus oxaliplatin (mIROX) is superior to irinotecan plus infusional 5-fluorouracil, leucovorin (FUFIRI) as first-line therapy of patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: A phase III, randomised, open-label multicentre study compared standard treatment with FUFIRI (irinotecan 80 mg/m(2), 5-fluorouracil 2000 mg/m(2), folinic acid 500 mg/m(2) weekly times 6) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85 mg/m(2) applied on days 1, 15 and 29 of a 7-week cycle. The primary end-point was progression-free survival (PFS). RESULTS: A total of 479 eligible patients were randomly assigned. Progression-free survival was 7.2 months in the mIROX arm and 8.2 months in the FUFIRI arm [hazard ratio=1.14; 95% confidence interval (CI) 0.94-1.37; P=0.178]. Comparable results were also obtained for overall survival time with 19 months in the mIROX-arm and 22 months in the FUFIRI-arm (hazard ratio=1.08, P=0.276). Both regimens induced an identical objective response rate (ORR) of 41%, but disease control rate (ORR plus stable disease) was significantly greater in the FUFIRI group (81% versus 68%, P=0.001). Most frequent grades 1-4 side-effects of mIROX and FUFIRI treatment were nausea (80% versus 73%) and delayed diarrhoea (79% versus 68%). Grades 3-4 toxicities were generally below 10%, except for diarrhoea which was more frequent in the mIROX-arm compared to the FUFIRI-arm (19% versus 30%, P=0.006) CONCLUSION: mIROX failed to show superior activity compared to high-dose 5-FU/folinic acid plus irinotecan. Due to better tolerability the combination of high-dose 5-FU/folinic acid and irinotecan remains a standard of care in first-line treatment of metastatic colorectal cancer.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Adenocarcinoma/pathology , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colonic Neoplasms/pathology , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Irinotecan , Leucovorin/administration & dosage , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Rectal Neoplasms/pathology , Young AdultABSTRACT
PURPOSE: This trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study. PATIENTS AND METHODS: Three hundred twelve patients with "aggressive" non-Hodgkin's lymphoma aged Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
, L-Lactate Dehydrogenase/blood
, Lymphoma, Non-Hodgkin/enzymology
, Lymphoma, Non-Hodgkin/therapy
, Stem Cell Transplantation
, Antineoplastic Combined Chemotherapy Protocols/administration & dosage
, Carmustine/administration & dosage
, Chemotherapy, Adjuvant
, Cyclophosphamide/administration & dosage
, Cytarabine/administration & dosage
, Doxorubicin/administration & dosage
, Drug Administration Schedule
, Etoposide/administration & dosage
, Female
, Germany
, Humans
, Lymphoma, Non-Hodgkin/drug therapy
, Lymphoma, Non-Hodgkin/radiotherapy
, Male
, Melphalan/administration & dosage
, Middle Aged
, Prednisolone/administration & dosage
, Prognosis
, Prospective Studies
, Radiotherapy, Adjuvant
, Risk
, Survival Analysis
, Transplantation, Autologous
, Treatment Outcome
, Vincristine/administration & dosage