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Original Contribution| Volume 3, ISSUE 4, P235-242, February 01, 2004

Phase III Study of Mitomycin-C with Protracted Venous Infusion or Circadian-Timed Infusion of 5-Fluorouracil in Advanced Colorectal Carcinoma

DOI:https://doi.org/10.3816/CCC.2004.n.004
Phase III Study of Mitomycin-C with Protracted Venous Infusion or Circadian-Timed Infusion of 5-Fluorouracil in Advanced Colorectal Carcinoma
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      Abstract

      The combination of protracted venous infusion (PVI) fluorouracil (5-FU) and mitomycin-C has previously been shown to be superior to PVI 5-FU alone in terms of response rate and failure-free survival. This study explores the effect of dose intensification by circadian timing of 5-FU in this combination on response, toxicity, and survival. Patients with advanced colorectal carcinoma were randomized to receive PVI 5-FU 300 mg/m2 daily or circadiantimed infusion (CTI) of 5-FU, beginning at 600 mg/m2 and subsequently reduced to 450 mg/m2, delivered as a flat-rate infusion from 10:15 PM to 9:45 AM. Both groups received mitomycin-C at a dose of 7 mg/m2 given every 6 weeks. From April 1996 to August 1998, 320 patients were randomized, including 263 with metastatic disease and 21 with circumferential margin involvement. The overall response rate for the PVI 5-FU group was 38%, compared with 30.3% for the CTI group (P = 0.176). There was no statistically significant difference in terms of failure-free survival (8.0 months vs. 9.9 months; P = 0.131) or overall survival (15.8 months vs. 16.3 months; P = 0.275) between the treatment groups. There were no differences in global quality of life. Grade 3/4 diarrhea occurred significantly more frequently with CTI 5-FU (6.5% vs. 19.8%; P < 0.001); a nonsignificant trend toward increased incidences of grade 3/4 infection and palmar—plantar erythema were observed with CTI 5-FU. This study confirms the high response rate and overall survival figures for the combination of PVI 5-FU and mitomycin-C in colorectal cancer. However, dose intensification of 5-FU using a circadian-timed, flat-rate infusion did not lead to improved response or survival.

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      References

        • Nordic Gastrointestinal Tumor Adjuvant Therapy Group
        Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: a randomized trial.
        J Clin Oncol. 1992; 10: 904-911
        • Scheithauer W
        • Rosen H
        • Kornek GV
        • et al.
        Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.
        BMJ. 1993; 306: 752-755
        • Beretta G
        • Bollina R
        • Martignoni G
        • et al.
        Fluorouracil + folates (FUFO) as standard treatment for advanced/metastatic gastrointestinal carcinoma (AGC).
        Ann Oncol. 1994; 5 (Abstract #239).: 239
        • Allen-Mersh T
        • Earlam S
        • Fordy C
        • et al.
        Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases.
        Lancet. 1994; 344: 1255-1260
        • Jonker DJ
        • Maroun JA
        • Kocha W
        Survival benefit of chemotherapy in metastatic colorectal cancer: a meta-analysis of randomized controlled trials.
        Br J Cancer. 2000; 82: 1789-1794
        • Lokich J
        • Ahlgren J
        • Gullo J
        • et al.
        A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study.
        J Clin Oncol. 1989; 7: 425-432
        • Hansen R
        • Ryan L
        • Anderson T
        • et al.
        Phase III study of bolus versus infusion fluorouracil with or without cisplatin in advanced colorectal cancer.
        J Natl Cancer Inst. 1996; 88: 668-674
        • Meta-analysis Group in Cancer
        Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.
        J Clin Oncol. 1998; 16: 301-308
        • Smaaland R
        • Laerum OD
        • Lote K
        • et al.
        DNA synthesis in human bone marrow is circadian stage dependent.
        Blood. 1991; 77: 2603-2611
        • Leavi F
        Chronopharmacology of anticancer agents.
        in: Lemmer B Handbook of experimental pharmacology: physiology and pharmacology of biological rhythms. Springr-Verlag, Berlin1997: 299-331
        • Harris BE
        • Song R
        • Soong SJ
        • et al.
        Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion.
        Cancer Res. 1990; 50: 197-201
        • Petit E
        • Milano G
        • Levi F
        • et al.
        Circadian rhythm-varying plasma concentration of 5-fluorouracil during a five-day continuous venous infusion at a constant rate in cancer patients.
        Cancer Res. 1988; 48: 1676-1679
        • Levi F
        Circadian chronotherapy for human cancers.
        Lancet Oncol. 2001; 2: 307-315
        • Levi FA
        • Zidani R
        • Vannetzel JM
        • et al.
        Chronomodulated versus fixed-infusion-rate delivery of ambulatory chemotherapy with oxaliplatin, fluorouracil, and folinic acid (leucovorin) in patients with colorectal cancer metastases: a randomized multi-institutional trial.
        J Natl Cancer Inst. 1994; 86: 1608-1617
        • Levi F
        • Zidani R
        • Misset JL
        Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. International Organization for Cancer Chronotherapy.
        Lancet. 1997; 350: 681-686
        • Klein F
        • Danober L
        • Roulon A
        • et al.
        Circadian rhythm in murine tolerance for the anticancer agent mitomycin-C (Mit-C).
        Ann Rev Chronopharmacol. 1989; 5: 367-370
        • Sothern RB
        • Haus R
        • Langevin T
        • et al.
        Profound circadian stage dependence of mitomycin-C toxicity.
        Ann Rev Chronopharmacol. 1989; 5: 389-392
        • Ross P
        • Norman A
        • Cunningham D
        • et al.
        A prospective randomised trial of protracted venous infusion 5-fluorouracil with or without mitomycin C in advanced colorectal cancer.
        Ann Oncol. 1997; 8: 995-1001
        • National Cancer Institute
        Guidelines for reporting adverse drug reactions. Division of Cancer Treatment, National Cancer Institute, Bethesda, MD1988
        • Miller AB
        • Hoogstraten B
        • Staquet M
        • et al.
        Reporting results of cancer treatment.
        Cancer. 1981; 47: 207-214
        • Adler S
        • Lang S
        • Langenmayer I
        • et al.
        Chronotherapy with 5-fluorouracil and folinic acid in advanced colorectal carcinoma.
        Cancer. 1994; 73: 2905-2912
        • Falcone A
        • Allegrini G
        • Antonuzzo A
        • et al.
        Infusions of fluorouracil and leucovorin: effects of the timing and semi-intermittency of drug delivery.
        Oncology. 1999; 57: 195-201
        • Cure H
        • Chevalier V
        • Adenis A
        • et al.
        Phase II trial of chronomodulated infusion of high-dose fluorouracil and l-folinic acid in previously untreated patients with metastatic colorectal cancer.
        J Clin Oncol. 2002; 20: 1175-1181
        • Giacchetti S
        • Perpoint B
        • Zidani R
        • et al.
        Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracilleucovorin as first-line treatment of metastatic colorectal cancer.
        J Clin Oncol. 2000; 18: 136-147
        • Ross P
        • Cunningham D
        Protracted 5-FU infusion.
        in: Wilke W Management of colorectal cancer. Martin Dunitz, London1997: 249-257
        • de Gramont A
        • Bosset JF
        • Milan C
        • et al.
        Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study.
        J Clin Oncol. 1997; 15: 808-815
        • Cunningham D
        • Glimelius B
        A phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluororacil therapy. V301 Study Group.
        Semin Oncol. 1999; 26: 6-12
        • Saltz LB
        • Cox JV
        • Blanke C
        • et al.
        Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group.
        N Engl J Med. 2000; 343: 905-914
        • Douillard JY
        • Cunningham D
        • Roth AD
        • et al.
        Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial.
        Lancet. 2000; 355: 1041-1047
        • de Gramont A
        • Figer A
        • Seymour M
        • et al.
        Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.
        J Clin Oncol. 2000; 18: 2938-2947
        • Rothenberg M
        • Oza A
        • Burger B
        • et al.
        Final results of a phase III trial of 5-FU/leucovorin versus oxaliplatin versus the combination in patients with metastatic colorectal cancer following irinotecan, 5-FU and leucovorin.
        Proc Am Soc Clin Oncol. 2003; 22 (Abstract #1011).: 252
        • Goldberg R
        • Morton R
        • Sargent DJ
        • et al.
        N9741: oxaliplatin (Oxal) or CPT-11 + 5-fluorouracil (5FU)/leucovorin (LV) or oxal + CPT-11 in advanced colorectal cancer (CRC). Updated efficacy and quality of life (QOL) data from an intergroup study.
        Proc Am Soc Clin Oncol. 2003; 22 (Abstract #1009).: 252
        • Tournigand C
        • Andre T
        • Achille E
        • et al.
        FOLFIRI followed by FOLFOX or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.
        Clin Oncol. 2004; 22: 229-237
        • Watkins D
        • Rao S
        • Cunningham D
        • et al.
        Capecitabine and mitomycin-C: an active low toxicity first line therapy in metastatic colorectal cancer (MCRC).
        Proc Am Soc Clin Oncol. 2003; 22 (Abstract #1109).: 276
        • Rao S
        • Watkins D
        • Hill M
        • et al.
        Capecitabine and mitomycin C (MMC) shows promising activity as a 3rd line agent in patients with metastatic colorectal carcinoma (MCRC) resistant to 5FU and irinotecan.
        Proc Am Soc Clin Oncol. 2003; 22 (Abstract #1286).: 320

      Article Info

      Publication History

      Accepted: January 28, 2004
      Received in revised form: January 14, 2004
      Received: July 29, 2003

      Footnotes

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      Identification

      DOI: https://doi.org/10.3816/CCC.2004.n.004

      Copyright

      © 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

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