Abstract
Purpose
Most stage II or III colorectal cancer patients are receiving nowadays a 4 to 6-month course of adjuvant chemotherapy. However, delays between cycles, reductions in the doses of chemotherapy drugs, or even permanent omissions of chemotherapy cycles might take place due to side effects or patient’s preference. We examined the impact of these treatment modifications on recurrence-free survival (RFS) and overall survival (OS).
Methods
We retrospectively collected data from colorectal cancer patients who had received adjuvant chemotherapy in our Department. Patients were categorized in five groups based on whether they had or not delays between chemotherapy cycles, dose reductions, and permanent omissions of chemotherapy cycles. Three-year RFS and OS of the five different groups were compared using the log-rank test and the Sidak approach.
Results
Five hundred and eight patients received treatment. Twenty seven percent of the patients had the full course of chemotherapy; the others had delays, dose reductions, or early termination of the treatment. No statistically significant differences were observed in 3-year RFS and OS between the five groups. A trend for worse RFS was noticed with early termination of treatment. A similar trend was also noticed for OS but only for stage II patients.
Conclusion
In colorectal cancer patients, receiving adjuvant chemotherapy, delays between chemotherapy cycles, dose reductions of chemotherapy drugs, or even early termination of the treatment course do not seem to have a negative impact in 3-year RFS and OS; however, due to the trend of worse RFS in patients receiving shorter courses of chemotherapy, further studies are needed.
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References
Cancer Research UK. Worldwide cancer statistics. Available from http://www.cancerresearchuk.org/cancer-info/cancerstats/world and accessed in June 2015.
Minicozzi P, Kaleci S, Maffei S, Allemani C, Giacomin A, Caldarella A, et al. Disease presentation, treatment and survival for Italian colorectal cancer patients: a EUROCARE high resolution study. Eur J Pub Health. 2014;24:98–100.
NCCN Guidelines, Colon cancer, 2014. Available from http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf and accessed in June 2015.
NCCN Guidelines, Rectal cancer, 2014. Available from http://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf and accessed in June 2015.
Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990;322:352–8.
O’Connell MJ, Mailliard JA, Kahn MJ, Macdonald JS, Haller DG, Mayer RJ, et al. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997;15:246–50.
O’Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou JI, Heise CP, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011;29:3381–8.
International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol. 1999;17:1356–63.
Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184–90.
Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, et al. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014;25:1356–62.
Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol. 2012;23:2479–516.
Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29:1465–71.
Pectasides D, Karavasilis V, Papaxoinis G, Gourgioti G, Makatsoris T, Raptou G, et al. Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer. BMC Cancer. 2015;15:384.
Smoragiewicz M, Javaheri KR, Yin Y, Gill S. Neutropenia and relative dose intensity on adjuvant FOLFOX chemotherapy are not associated with survival for resected colon cancer. J Gastrointest Cancer. 2014;45:460–5.
Aspinall SL, Good CB, Zhao X, Cunningham FE, Heron BB, Geraci M, et al. Adjuvant chemotherapy for stage III colon cancer: relative dose intensity and survival among veterans. BMC Cancer. 2015;15:62.
Chau I, Norman AR, Cunningham D, Tait D, Ross PJ, Iveson T, et al. A randomised comparison between 6 months of bolus fluorouracil/leucovorin and 12 weeks of protracted venous infusion fluorouracil as adjuvant treatment in colorectal cancer. Ann Oncol. 2005;16:549–57.
ClinicalTrials.gov. Available from http://ClinicalTrials.gov and accessed in June 2015.
Peto R, Peto J. Asymptotically efficient rank invariant test procedures. J R Stat Soc A. 1972;135:185–98.
Šidák ZK. Rectangular confidence regions for the means of multivariate normal distributions. J Am Stat Assoc. 1967;62:626–33.
Kaplan E, Meier P. Non parametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
Papadimitriou CA, Papakostas P, Karina M, Malettou L, Dimopoulos MA, Pentheroudakis G, et al. A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study. BMC Med. 2011;9:10.
André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.
Abrams TA, Brightly R, Mao J, Kirkner G, Meyerhardt JA, Schrag D, et al. Patterns of adjuvant chemotherapy use in a population-based cohort of patients with resected stage II or III colon cancer. J Clin Oncol. 2011;29:3255–62.
Ho J, Gill S, Woods R, Kennecke HF. Association of survival outcomes with dose intensity of adjuvant therapy with capecitabine for colorectal cancer. J Clin Oncol. 2010;28 Suppl 15:3624.
André T, Iveson T, Labianca R, Meyerhardt JA, Souglakos I, Yoshino T, et al. The IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration: prospective combined analysis of phase III trials investigating duration of adjuvant therapy with the FOLFOX (FOLFOX4 or modified FOLFOX6) or XELOX (3 versus 6 months) regimen for patients with stage III colon cancer: trial design and current status. Curr Colorectal Cancer Rep. 2013;9:261–9.
Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 2011;305:2335–42.
Des Guetz G, Nicolas P, Perret GY, Morere JF, Uzzan B. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer. 2010;46:1049–55.
Acknowledgments
The authors would like to thank Georgia Kiosse, Data Manager at the Clinical Trials Unit of the 3rd Medical Oncology Department of “Agii Anargiri” General Cancer Hospital, for her support and hard work. This work was supported by a research grant from Amgen Greece.
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Sgouros, J., Aravantinos, G., Kouvatseas, G. et al. Impact of Dose Reductions, Delays Between Chemotherapy Cycles, and/or Shorter Courses of Adjuvant Chemotherapy in Stage II and III Colorectal Cancer Patients: a Single-Center Retrospective Study. J Gastrointest Canc 46, 343–349 (2015). https://doi.org/10.1007/s12029-015-9746-8
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DOI: https://doi.org/10.1007/s12029-015-9746-8