Response to Neo-Adjuvant Chemotherapy for Colorectal Cancer Liver Metastases: A Key for Improving Survival?

e15015 Background: Hepatic resection is one of the treatment strategies for resectable colorectal cancer liver metastases (CLM). The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable CLM is still unclear. Adjuvant chemotherapy consisting of capecitabine plus oxaliplatin (CapeOx) appears to be equivalent to FOLFOX in patients with stage III colon cancer. Furthermore, some studies suggest that adjuvant chemotherapy for three months after curative resection for stage II/III colorectal cancer has equivalent efficacy to adjuvant chemotherapy for 6 months. We initiated a multi-institutional, single-arm, open label, phase II trial to confirm the feasibility of adjuvant CapeOx for three months for post curative resection of CLM. Methods: Patients received one course of capecitabine followed by four courses of CapeOx for a total five courses (15 weeks) as adjuvant chemotherapy after curative resection of CLM. CapeOx consisted of a 2-hour intravenous infusion of oxaliplatin 130 mg/m2 on day 1 plus oral capecitabine 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle. The primary endpoint was completion rate of adjuvant chemotherapy. We set a threshold completion rate of protocol treatment of 45% and an expected completion rate of 70%. Given a one-sided α of 0.1 and statistical power of 80%, a minimum of 25 patients was required. Results: From May 2013 to November 2015, Twenty-eight patients were enrolled from six institutions: median age 69.5y, 54% male, 78.5% left-sided primary. Of the patients, 15 were synchronous metastases and 13 were metachronous. The locations of the metastases were unilobar in 20 patients and bilobar in 8. The mean number of lesions resected was two (range, 1 to 4). The mean size of largest tumor was 31 mm (range, 2 to 112 mm). Among the 28 patients, 20 (71.4 %: 95% CI, 53.6 to 89.3%) completed the protocol treatment. The most common grade 3 or 4 toxicities were neutropenia (29%). No treatment related death was observed. Conclusions: Adjuvant CapeOx for three months for post curative resection of CLM was feasible. Clinical trial information: UMIN000011164.

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Oral adjuvant chemotherapy using uracil-tegafur (UFT) with leucovorin (LV) after resection of colorectal cancer liver metastases: Long-term survival results of the phase III UFT/LV study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.672 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 672-672 ◽

Cited By ~ 3

Author(s):

Kiyoshi Hasegawa ◽

Akio Saiura ◽

Tadatoshi Takayama ◽

Shinichi Miyagawa ◽

Junji Yamamoto ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Liver Metastases ◽

Curative Resection ◽

Phase Iii ◽

Control Group ◽

Colorectal Cancer Liver Metastases ◽

The Impact ◽

Better Than

672 Background: Surgical resection has been accepted as the standard therapy for colorectal cancer liver metastases (CRLM), however, high recurrence incidence even after curative resection remains a severe problem. The 1st analysis of the UFT/LV trial showed that oral UFT/LV for 6 months significantly prolonged relapse-free survival (RFS) after resection for CRLM (Kobayashi A et al. ASCO 2014, Hasegawa K et al. PlosOne 2016 E-pub). To further evaluate the impact of the UFT/LV therapy on overall survival (OS), we performed the 2nd analysis under longer follow-up period, as have been scheduled by the protocol. Methods: Patients undergoing curative resection of CRLM were randomly assigned to either UFT/LV or surgery alone (control) group. In the UFT/LV group, 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75 mg/day for 28 days followed by 7 days rest in one cycle) were administered. Results: Between 2004 and 2010, a total of 180 patients were enrolled to this trial, among whom 3 patients were ineligible for analysis. Median follow-up of the 2nd analysis was 6 years. The 5y-OS rate in the UFT/LV group was 65.3%, which was slightly better than the control group (62.2%) without statistical significance. The hazard ratio for death in the UFT/LV relative to the control was 0.86 (95% confidence interval: 0.54-1.38, P = 0.54). The OS curves of the 2 groups were identical within 4 years after resection, however, the OS curve of the UFT/LV group seemed to go higher than the control group. The 5y-RFS rate in the UFT/LV group was 36.2%, which was significantly better than that in the control group (32.3%), as have been shown by the 1st analysis. Conclusions: The results of the 2nd analysis suggested that oral UFT/LV adjuvant chemotherapy might be also useful to prolong OS, as have been confirmed for RFS. This regimen can be recommended as an alternative choice after hepatic resection for CRLM. Clinical trial information: C000000013.

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Survival results of hepatectomy followed by adjuvant chemotherapy with three months of capecitabine plus oxaliplatin for colorectal cancer liver metastases: A multicenter phase II study.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.866 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 866-866 ◽

Cited By ~ 1

Author(s):

Hironaga Satake ◽

Hiroki Hashida ◽

Hiroaki Tanioka ◽

Yasuhiro Miyake ◽

Shinichi Yoshioka ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Liver Metastases ◽

Phase Ii ◽

Curative Resection ◽

Completion Rate ◽

Colorectal Cancer Liver Metastases ◽

Oral Capecitabine ◽

Stage Iii Colon Cancer

866 Background: Hepatic resection is one of the treatment strategies for resectable colorectal cancer liver metastases (CLM). The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable CLM is still unclear. Adjuvant chemotherapy consisting of capecitabine plus oxaliplatin (CapeOx) appears to be equivalent to FOLFOX in patients with stage III colon cancer. Furthermore, the IDEA collaboration reported that adjuvant chemotherapy with the three months of CapeOx after curative resection for stage III colon cancer has equivalent efficacy to adjuvant chemotherapy for 6 months. We conducted a multi-institutional, single-arm, phase II trial to confirm the feasibility of the three months of adjuvant CapeOx for post curative resection of CLM. Methods: Patients received one course of capecitabine followed by four courses of CapeOx for a total five courses (15 weeks) as adjuvant chemotherapy after curative resection of CLM. Oral capecitabine was given with 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle, and CapeOx consisted of oral capecitabine plus oxaliplatin 130 mg/m2 on day 1 in a 3-week cycle. The primary endpoint was completion rate of adjuvant chemotherapy. We set a threshold completion rate of protocol treatment of 45% and an expected completion rate of 70%. Given a one-sided α of 0.1 and statistical power of 80%, a minimum of 25 patients was required. Results: From May 2013 to November 2015, Twenty-eight patients were enrolled from six institutions: median age 69.5y, 54% male, 78.5% left-sided primary. Of the patients, 15 were synchronous metastases and 13 were metachronous. The locations of the metastases were unilobar in 20 patients and bilobar in 8. The mean number of lesions resected was two (range, 1 to 4). Among the 28 patients, 20 (71.4%: 95% CI, 53.6 to 89.3%) completed the protocol treatment. The most common grade 3/4 toxicities were neutropenia (29%). No treatment related death was observed. With a median follow-up period of 36 months (range 15-53months), 3 year-relapse free survival was 75.3%. Conclusions: The three months of adjuvant CapeOx is tolerable for post curative resection of CLM. Clinical trial information: 000011164.

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