Hepatic arterial chemotherapy with raltitrexed and oxaliplatin versus standard chemotherapy in unresectable liver metastases from colorectal cancer after conventional chemotherapy failure (HEARTO): a randomized phase-II study

14549 Background: To determine the maximum-tolerated dose (MTD) and to evaluate the efficacy and tolerability of combination chemotherapy of irinotecan (CPT-11), UFT and leucovorin (LV) with hepatic arterial infusion (HAI) in colorectal cancer patients with unresectable liver metastases. Methods: Patients who had unresectable liver metastases from colorectal cancer were treated concurrently with intravenous CPT-11 on day1 of each 14-day treatment cycle with dose escalation, with orally UFT and LV on day 1–7 of each cycle, and with HAI of 5-FU on day 8–14 of each cycle. The primary objective of this phase I study was to determine the MTD of biweekly intravenous CPT-11 and UFT/LV with HAI of 5-FU. In the phase II study, the primary endpoint was to determine the response rate. Results: In the phase I study, the recommended dose of CPT-11 for phase II study was 140 mg/m2 combined with UFT 300 mg/m2/day, LV 75 mg/body/day and 5-FU 2,000 mg/body/week. Sixteen patients were enrolled onto the phase II study. The six patients treated at the recommended dose during the phase I study also included in the phase II analysis (n = 22). Median number of liver metastases was 12 (range, 3 to 35). Median size of maximum diameter was 6.3 cm (range, 2.0 to 12.0 cm). The most common adverse event was neutropenia. The complete and partial response rate totaled 81.8%. Median survival time has not been reached yet. Eleven patients (50.0%) were ultimately able to undergo liver resection. Conclusions: The combination chemotherapy of CPT-11 and UFT/LV with HAI was safe, well tolerate and effective in current population of the patients with unresectable liver metastases from colorectal cancer. Updated toxicity and response data will be available in the spring of 2007. No significant financial relationships to disclose.

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Randomized Phase II Study of 5-Fluorouracil Hepatic Arterial Infusion with or without Antineoplastons as an Adjuvant Therapy after Hepatectomy for Liver Metastases from Colorectal Cancer

PLoS ONE ◽

10.1371/journal.pone.0120064 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0120064 ◽

Cited By ~ 5

Author(s):

Yutaka Ogata ◽

Keiko Matono ◽

Hideaki Tsuda ◽

Masataka Ushijima ◽

Shinji Uchida ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Therapy ◽

Liver Metastases ◽

Phase Ii ◽

Phase Ii Study ◽

Hepatic Arterial Infusion ◽

Arterial Infusion ◽

Randomized Phase Ii

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The ATOM trial: A multicenter, randomized phase II study of modified FOLFOX6 plus bevacizumab and modified FOLFOX6 plus cetuximab for colorectal cancer with liver-limited metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.tps777 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. TPS777-TPS777 ◽

Cited By ~ 1

Author(s):

Yasunori Emi ◽

Kei Muro ◽

Takeharu Yamanaka ◽

Yu Katayose ◽

Hiroyuki Uetake ◽

...

Keyword(s):

Colorectal Cancer ◽

Growth Factor ◽

Liver Metastases ◽

Phase Ii ◽

Phase Ii Study ◽

Tumor Diameter ◽

Exon 2 ◽

Metastatic Lesions ◽

Randomized Phase Ii ◽

Modified Folfox6

TPS777 Background: It remains unresolved which antibody, anti-vascular endothelial growth factor or anti-epidermal growth factor receptor antibody, is the best targeted agent to combine with chemotherapy for patients having liver-limited metastases of KRAS Exon 2 or RAS wild-type colorectal cancer. Methods: The ATOM trial is a Japanese multicenter, randomized phase II study comparing modified FOLFOX6 plus bevacizumab with modified FOLFOX6 plus cetuximab in patients with unsuitable liver metastases for resection (5 or more liver metastatic lesions and/or maximum tumor diameter > 5cm). Patients are enrolled and randomly assigned to receive either treatment in 1:1 ratio from May 2013 to April 2016. Stratification factors for randomization are synchronous or metachronous liver metastases, number (1–4 or ≥ 5) and size ( ≤ 5 cm or > 5 cm) of metastatic lesions, and adjuvant chemotherapy with or without oxaliplatin-containing regimen. All patients are to be followed up to March 2017. Primary endpoint is progression-free survival (PFS). We employed a selection design based on hazard ratios. Planned sample size is 120 patients with 84 estimated PFS events based on the hypothesis to select the superior treatment with the 75.0 % selection probability if the difference of both treatments is a 1-year PFS rate of 5% and the inferior treatment has a 1-year PFS rate of 50%. Secondary endpoints are response rate, tumor shrinkage at week 8, liver resection rate, time to treatment failure, overall survival, quality of life, and adverse events. Exploratory endpoints include pathologic and morphologic assessments, which will be investigated in collaboration with radiologists and pathologists. The plasma factors relating to tumor angiogenesis are assessed sequentially to explore the association with treatment efficacies. As of Aug 20th 2015, 102 patients were enrolled. The results from this trial will show which targeted agents should be used to treat liver-limited diseases from colorectal cancer with WT RAS tumor. Clinical trial information: NCT01836653.

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Percutaneous laser ablation in patients with isolated unresectable liver metastases from colorectal cancer: Results of a phase II study

Acta Oncologica ◽

10.1080/02841860500438029 ◽

2006 ◽

Vol 45 (1) ◽

pp. 77-83 ◽

Cited By ~ 24

Author(s):

Claudio M. Pacella ◽

Dario Valle ◽

Giancarlo Bizzarri ◽

Sara Pacella ◽

Maurizio Brunetti ◽

...

Keyword(s):

Colorectal Cancer ◽

Laser Ablation ◽

Liver Metastases ◽

Phase Ii ◽

Phase Ii Study ◽

Unresectable Liver Metastases ◽

Percutaneous Laser Ablation

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Randomized Multicenter Phase II Study Comparing a Combination of Fluorouracil and Folinic Acid and Alternating Irinotecan and Oxaliplatin With Oxaliplatin and Irinotecan in Fluorouracil-Pretreated Metastatic Colorectal Cancer Patients

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.22.4195 ◽

2001 ◽

Vol 19 (22) ◽

pp. 4195-4201 ◽

Cited By ~ 47

Author(s):

Yves Bécouarn ◽

Erick Gamelin ◽

Bruno Coudert ◽

Sylvie Négrier ◽

Jean-Yves Pierga ◽

...

Keyword(s):

Colorectal Cancer ◽

Folinic Acid ◽

Phase Ii ◽

Phase Ii Study ◽

Survival Times ◽

Activity Data ◽

Randomized Phase Ii ◽

Grade 3 ◽

Intent To Treat ◽

Colorectal Cancer Patients

PURPOSE: To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination. PATIENTS AND METHODS: Sixty-two patients were treated: arm FC/FO (32 patients) received, every 4 weeks, FA 200 mg/m2 followed by a 400-mg/m2 5-FU bolus injection, then a 600-mg/m2 continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m2 on day 1) and oxaliplatin (85 mg/m2 on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m2 and irinotecan 200 mg/m2 every 3 weeks. RESULTS: In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bitherapy regimen. Median progression-free and overall survival times were 8.2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-related deaths occurred. CONCLUSION: The every-3-weeks OC combination is safe and active in advanced 5-FU–resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.

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