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Investigational New Drugs

, Volume 24, Issue 5, pp 447–454 | Cite as

Phase II study of mitomycin-C, adriamycin, cisplatin (MAP) and Bleomycin-CCNU in patients with advanced cancer of the anal canal: An eastern cooperative oncology group study E7282

  • Minaxi Jhawer
  • Sridhar Mani
  • Myrto Lefkopoulou
  • Richard G. Hahn
  • Jules Harris
  • Paul J. Catalano
  • Daniel Haller
Phase II Studies

Summary

Metastatic anal cancer is a rare disease in the Western hemisphere and current treatment modalities are not effective. In this study, patients with advanced epithelial cancer of the anal canal received MAP followed by Bleomycin and CCNU upon progression of disease. Twelve out of twenty eligible patients had a partial response 60%, (95% CI {36% −81%}). No complete responses were observed. The median survival was 15 months (95% CI {6–20} months). The median time to progression or death was 8 months (95% CI {4–9 months}). Toxicities were moderate and tolerable with routine supportive care; there were 2 cases of grade 3 vomiting, 2 cases of respiratory distress (one grade 1 and one grade 3), one case each of grade 3 leg cramps and cardiac arrhythmia. Of particular note were 7 cases of grade 3 hematologic toxicity. Two patients had grade 4 leukopenia and thrombocytopenia, respectively, that resolved without sequelae. The combination therapy of MAP followed by Bleomycin and CCNU for patients with advanced anal cancer, not amenable to radiotherapy or surgery, results in a moderate objective response but with moderate toxicities. This regimen and sequence is worthy of further study especially in combination with colony stimulating factors, however, its tolerability may be most applicable for patients who have had minimal prior therapy.

Keywords

Anal cancer Mitomycin-C Adriamycin Cisplatin Bleomycin CCNU Phase II 

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References

  1. 1.
    Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics. CA Cancer J Clin 55(1):10–30PubMedCrossRefGoogle Scholar
  2. 2.
    Failes D, Morgan BP (1973) Squamous cell carcinoma of the anus. Dis Colon Rectum 16:397–401PubMedGoogle Scholar
  3. 3.
    Dalby JE, Pointou RS (1961) Treatment of anal carcinoma by interstitial radiation. AJR 85:515–520Google Scholar
  4. 4.
    Nigro N (1987) Multidisciplinary management of cancer of the anus. World J Surg 11:446–451PubMedCrossRefGoogle Scholar
  5. 5.
    UKCCCR Anal Cancer Trial Working Party (1996) Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and Mitomycin. Lancet 348:1049–1054CrossRefGoogle Scholar
  6. 6.
    Pahlman L, Glimelius B, Goldman S (1988) Management of epidermoid carcinoma of the anus. Ups J Med Sci 93(2):179–185PubMedCrossRefGoogle Scholar
  7. 7.
    Haddock MG, Martenson JA (1998) Anal carcinoma. Cancer Treat Res 98:201–225PubMedGoogle Scholar
  8. 8.
    Cummings BJ (1996) Anal canal cancer: current treatment and results. Ann Acad Med Singapore 25(3):460–467PubMedGoogle Scholar
  9. 9.
    Lindell TD, Moseley S, Fletcher WS (1974) Combination CCNU and Bleomycin therapy for squamous cell carcinoma. Am Surg 40:281–289PubMedGoogle Scholar
  10. 10.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  11. 11.
    Brookmeyer R, Crowley J (1982) A confidence interval for the median survival time. Biometrics 38:29–41Google Scholar
  12. 12.
    CTC Manual CTEP Web site. http://ctep.info.nih.gov/CTC3/ctc.htmGoogle Scholar
  13. 13.
    Allal AS, Laurencet FM, Reymond MA, Kurtz JM, Marti MC (1999) Effectiveness of surgical salvage therapy for patients with locally uncontrolled anal carcinoma after sphincter-conserving treatment. Cancer 86(3):405–409CrossRefGoogle Scholar
  14. 14.
    Shimizu Y, Akiyama F, Umezawa S, Ishiya T, Utsugi K, Hasumi K (1998) Combination of consecutive low-dose cisplatin with Bleomycin, Vincristine, and Mitomycin for recurrentcervical carcinoma. J Clin Oncol 16(5):1869–1878Google Scholar
  15. 15.
    Ong ST, Vogelzang NJ (1996) Chemotherapy in malignant pleural mesothelioma. Areview. J Clin Oncol 14(3):1007–1017Google Scholar
  16. 16.
    Smith HO, Stringer CA, Kavanagh JJ, Gershenson DM, Edwards CL, Wharton JT (1993) Treatment of advanced or recurrent squamous cell carcinoma of the uterine cervix with Mitomycin-C,Bleomycin, and Cisplatin chemotherapy. Gynecol Oncol 48(1):11–15CrossRefGoogle Scholar
  17. 17.
    Hoffman MS, Kavanagh JJ, Roberts WS, LaPolla JP, Fiorica JV, Hewitt S, Cavanagh DA (1991) Phase II evaluation of cisplatin, Bleomycin, and Mitomycin-C in patients with recurrent squamous cell carcinoma of the cervix. Gynecol Oncol 40(2):144–146CrossRefGoogle Scholar
  18. 18.
    Pennucci MC, Ardizzoni A, Pronzato P, Fioretti M, Lanfranco C, Verna A, Giorgi G, Vigani A, Frola C, Rosso R (1997) Combined Cisplatin, Doxorubicin, and Mitomycin for the treatment of advanced pleural mesothelioma: a phase II FONICAP trial. Italian Lung Cancer Task Force. Cancer 79(10):1897–1902CrossRefGoogle Scholar
  19. 19.
    De Lisi V, Cocconi G, Angelini F, Cavicchi F, Di Costanzo F, Gilli G, Rodino C, Soldani M, Tonato M, Finardi C (1996) The combination of Cisplatin, Doxorubicin, and Mitomycin (PAM) compared with the FAM regimen in treating advanced gastric carcinoma. A phase II randomized trial of the Italian Oncology Group for Clinical Research. Cancer 77(2):245–250CrossRefGoogle Scholar
  20. 20.
    Chahinian AP, Antman K, Goutsou M, Corson JM, Suzuki Y, Modeas C, Herndon JE II,Aisner J, Ellison RR, Leone L, et al (1993) Randomized phase II trial of cisplatin with Mitomycin-C orDoxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B. J Clin Oncol 11(8):1559–1565Google Scholar
  21. 21.
    Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, Parkinson DR (1993) Randomized comparison of Doxorubicin alone versus Ifosfamide plus Doxorubicin or Mitomycin-C, Doxorubicin, and Cisplatin against advanced soft tissue sarcomas. J Clin Oncol 11(7):1269–1275Google Scholar
  22. 22.
    Eagan RT, Therneau TM, Rubin J, Long HJ, Schutt AJ (1987) Lack of value for Cisplatin added toMitomycin-Doxorubicin combination chemotherapy for carcinoma of unknown primary site. A randomized trial. Am J Clin Oncol 10(1):82–85Google Scholar
  23. 23.
    Nakano H, Kurihara M, Saito R, Takise A, Tsuchiya S, Minato K, Takehara K, Saruya T,Kuwabara H, Fueki R, et al (1986) [Combination chemotherapy with cis-platinum, Adriamycin and Mitomycin-C C (PAM) in the treatment of non-small cell carcinoma of the lung]. Gan To Kagaku Ryoho 13(6):2123–2127Google Scholar
  24. 24.
    Creagan ET, Chang M, Long HJ, Rubin J (1986) A phase II clinical trial of the combination Mitomycin-C, Adriamycin, and Cis-diamminedichloroplatinum in patients with advanced upper aerodigestive cancer. Head Neck Surg 8(3):153–158Google Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Minaxi Jhawer
    • 1
  • Sridhar Mani
    • 1
  • Myrto Lefkopoulou
    • 2
  • Richard G. Hahn
    • 3
  • Jules Harris
    • 4
  • Paul J. Catalano
    • 2
  • Daniel Haller
    • 5
  1. 1.Department of OncologyMontefiore Medical Center, Weiler HospitalBronx10461
  2. 2.Dana-Farber Cancer InstituteBoston
  3. 3.Mayo ClinicRochester
  4. 4.Rush PresbyterianSt. Luke’s Medical CenterChicago
  5. 5.University of Pennsylvania Cancer CenterPhiladelphia

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