Phase III Trial of Capecitabine Plus Oxaliplatin As Adjuvant Therapy for Stage III Colon Cancer: A Planned Safety Analysis in 1,864 Patients

Schmoll, Hans Joachim; Cartwright, Thomas H.; Tabernero, Josep; Nowacki, Marek P.; Figer, Arié; Maroun, J.; Price, Tim; Lim, Robert; Cutsem, Éric Van; Park, Young Suk; McKendrick, Joseph; Topham, Claire; Soler-González, Gemma; Braud, Filippo de; Hill, Mark; Sirzén, Florin; Haller, Daniel G.

doi:10.1200/jco.2006.08.1075

Cited by 267 publications

(177 citation statements)

References 16 publications

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“…Toxicity profiles of FOLFOX and FOLFIRI (Andre et al, 2004;O'Connell, 2004;Allegra and Sargent, 2005) may reduce the completion of these treatments, but fewer cycles of these regimes may be as efficacious as the completed Mayo regime. A recently published safety analysis of the XELOX NO16968 study (Schmoll et al, 2007) found more frequent treatment discontinuations with XELOX compared to the FU/LV Mayo and Roswell Park regimes; however a comparable number of patients completed 12 weeks of therapy (88 and 82%, respectively).…”

Section: Discussionmentioning

confidence: 95%

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

et al. 2007

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Two recent North American studies have shown that completion of 5-fluorouracil (5FU)-based adjuvant chemotherapy is a major prognostic factor for the survival of elderly stage III colon cancer patients. The aim of the present study was to confirm this finding in a population-based series from Australia. The study cohort comprised 851 stage III colon cancer patients treated by surgery alone and 461 who initiated the Mayo chemotherapy regime. One-third of patients who initiated chemotherapy failed to complete more than three cycles of treatment. Independent predictors for failure to complete were treatment in district or rural hospitals, low socioeconomic index and treatment by a low-volume surgeon. Patients who failed to complete chemotherapy showed worse cancer-specific survival compared not only to those who completed treatment (HR ¼ 2.24; 95% confidence interval (CI) (1.66 -3.03), Po0.001) but also to those treated by surgery alone (HR ¼ 1.37; 95% CI (1.09 -1.72), P ¼ 0.008). The current and previous studies demonstrate the importance of completing adjuvant 5-FU-based chemotherapy for colon cancer. Further prospective studies are required to identify better the physiological and socioeconomic factors responsible for failure to complete chemotherapy so that appropriate improvements in health service delivery can be made.

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Section: Discussionmentioning

confidence: 95%

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

et al. 2007

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“…Despite recent advances in the development of various diagnostic tools, in many patients, colorectal cancer is still diagnosed at an advanced stage, and recurrent tumors are often detected even after curative surgery. On the other hand, new chemotherapeutic regimens such as FOLFOX, FOLFIRI, and XELOX have been developed to exert a more potent activity 3, 4, 5, 6. More recently, molecular targeted therapies such as tyrosine kinase inhibitors and monoclonal antibodies have been shown to enhance tumor regression in combination with chemotherapy 7, 8…”

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confidence: 99%

Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status

Kato

Futamura

Kanematsu

et al. 2015

Intl Journal of Cancer

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Targeted molecular therapy is an effective anticancer strategy. Anti‐EGFR monoclonal antibodies such as cetuximab (CTX) have been approved for the treatment of various malignancies, including colorectal cancer (CRC) with wild‐type KRAS. However, their efficacy in patients with KRAS mutations has not been established. Therefore, we investigated whether CTX treatment was effective as a single agent or in combination with zoledronic acid (ZOL) in human CRC cell lines with different KRAS status. CRC cell lines SW48 (wild‐type KRAS) and LS174T (mutant KRAS) were treated with ZOL, CTX and a combination of both drugs. Cytotoxicity was measured using the MTT assay. Changes in the levels of intracellular signaling proteins were evaluated using western blot analysis. Finally, we evaluated the efficacy of the combination treatment in an in vivo xenograft model. We observed that ZOL apparently inhibited growth in both cell lines, whereas CTX showed little effect. ZOL also increased the levels of unprenylated RAS. Combined ZOL and CTX treatment was synergistic in both cell lines and was associated with inhibition of the RAS‐MAPK and AKT‐mTOR signaling pathways. Furthermore, the combination treatment was more effective in suppressing the growth of xenografts derived from both SW48 and LS174T cells; this effect was associated with increased apoptosis. These results demonstrate that ZOL inhibits the growth of colon cancer cells regardless of KRAS status, and combination therapy using ZOL and CTX enhances this growth suppression. These findings suggest a novel strategy for the treatment of CRC independent of KRAS mutational status.

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“…More importantly, our study provides preliminary survival data to support the efficacy of XELOX in the adjuvant setting. There are two published trials showing a favourable survival outcome and tolerability associated with the use of XELOX in the adjuvant setting (Schmoll et al, 2007;Haller et al, 2011). However, our study contained a wider range of standard (non-trial) patients than in controlled clinical studies, thus better representing the reality of everyday clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Tolerability of Adjuvant Oral Capecitabine plus Intravenous Oxaliplatin (XELOX) in Asian Patients with Colorectal Cancer: 4-Year Analysis

Chiu

Tang²,

Leung³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Although FOLFOX (infusional fluorouracil/leucovorin plus oxaliplatin) is established as a standard chemotherapeutic regimen, the long term efficacy of adjuvant XELOX (oral capecitabine plus intravenous oxaliplatin) in Asian colorectal cancer (CRC) patients remains anecdotal. Moreover, uncertainties persist as to whether pharmacogenetic differences in Asian populations preclude equally tolerable and effective administration of these drugs. Method: One hundred consecutive patients with resected colorectal cancer received adjuvant XELOX (oxaliplatin 130 mg/m 2 on day 1 plus capecitabine 900 mg/m 2 twice daily on day 1 to 14 every 3 weeks for 8 cycles) at Queen Mary Hospital, Hong Kong. Endpoints monitored during follow-up were disease-free survival (DFS) and disease recurrence, overall survival (OS) and adverse events (AEs). Results: The median patient age was 56 years, 56% were diagnosed with rectal cancer and 44% with colonic cancer. After a median follow-up of 4.3 years (95% confidence interval, 3.2-4.7), 24 recurrences were confirmed including 13 patients who died due to progressive disease. Four-year DFS was 81% in colon cancer patients and 67% in rectal cancer patients (p=0.06 by log-rank test). For the cohort as a whole, OS was 90% at 3 years and 84% at 5 years. Treatment-related AEs led to early withdrawal in four patients. The commonest non-hematological AEs were neuropathy (91%), hand-foot syndrome (49%) and diarrhea (46%), while the commonest grade 3/4 AEs were neutropenia (11%) and diarrhea (10%). Conclusion: These results confirm the favourable long term survival benefit with good tolerability in using adjuvant XELOX in treating East Asian colorectal cancer patients.

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Phase III Trial of Capecitabine Plus Oxaliplatin As Adjuvant Therapy for Stage III Colon Cancer: A Planned Safety Analysis in 1,864 Patients

Abstract: XELOX has a manageable tolerability profile in the adjuvant setting. Efficacy data will be available within the next 24 months.

Cited by 267 publications

References 16 publications

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status

Efficacy and Tolerability of Adjuvant Oral Capecitabine plus Intravenous Oxaliplatin (XELOX) in Asian Patients with Colorectal Cancer: 4-Year Analysis

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