Aims and Background: Irinotecan is a standard option for relapsed/refractory advanced colo- rectal cancer. Combination with raltitrexed and irinotecan at lower than MTD doses should preserve disease stabilisation while decreasing toxicity. Patients and Methods: From January 2004 to April 2009, we analyzed, retrospectively, our data on irinotecan + raltitrexed, fixed doses, as a second-line chemotherapy in elderly pa- tients (>70 years) with advanced colorectal can- cer after failure of oxaliplatin based chemothera- py twenty-three patients were evaluated. Iri- notecan 350 mg + raltitrexed 2.6 mg were given every 3 weeks. Tumo r measurements were ob- tained after every third course of therapy. Toxic- ity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, ver- sion 2. Results: The median number of treatment courses received per patient was 4 (range, 1 - 8). All pa-tients were assessable for toxicity and 21 for response. The most frequently observed severetoxicities were diarrhea (grade 2, 13%) No cases of significant neutropenia occurred. Ob- jective partial responses were observed in 3 pa- tients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time- to-progression of 4.3 months and a median sur- vival of 8.3 months. Conclusions: A three weekly irinotecan + raltitrexed administration can indu- ce tumor control in elderly patients with advanc- ed colorectalcancer that has progressed during or shortly after oxaliplatin-based chemotherapy. The diarrhea by irinotecan, seems mitigated by coad-ministration of a smaller dose of raltitrexed
References
[1]
Cunningham, D., Pyrh?nen, S., James, R.D., Punt, C.J.A., Hickish, T.F., Heikkila, R., Johannesenm, T.B., Starkhammar, H., Thopam, C.A., Awad, L., Jacques, C. and Herait, P. (1998) Randomised trial of irinotecan plus supportive care versus supportive care alone after fluor- ouracil failure for patients with metastatic colorectal cancer. Lancet, 352, 1413-1418.
[2]
Rougier, P, Van Cutsem, E., Bajetta, E., Niederle, N., Possinger, K., Labianca, R., Navarro, M., Morant, R., Bleiberg, H., Wils, J., Awad, L., Herait, P. and Jacques, C. (1998) Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet, 352, 1407-1412.
[3]
Armand, J.P., Ducreux, M., Mahjoubi, M., Abigerges, D., Bugat, R., Chabot, G., Herait, P., De Forni, M. and Rougier, P. (1995) CPT-11 (irinotecan) in the treatment of colorectal cancer. European Journal of Cancer, 31A, 1283-1287.
[4]
Pitot, H.C., Wender, D.B., O’Connell, M.J., Schroeder, G., Goldberg, R.M., Rubin, J., Mailliard, J.A., Knost, J.A., Ghosh, C., Kirschling, R.J., Levitt, R. and Windschitl, H.E. (1997) Phase II trial ofirinotecan in patients with metastatic colorectal carcinoma. Journal of Clinical Oncology, 15, 2910-2919.
[5]
Rothenberg, M.L., Cox, J.V., De Vore, R.F., Hainsworth, J.D., Pazdur, R., Rivkin, S.E., Macdonald, J.S., Geyer, C.E., Sandbach, J., Wolf, D.L., Mohrland, J.S., Elfring, G.L., Miller, L.L. and Von Hoff, D.D. (1999) A multicenter, phase II trial of weekly irinotecan (CPT-11) inpatients with previously treated colorectal carcinoma. Cancer, 85, 786-795.
[6]
Schoemaker, N.E., Kuppens, I.E.L.M., Moiseyenko, V., Glimelius, B., Kjaer, M., Starkhammer, H., Richel, D.J., Smaaland, R., Bertelsen, K., Poulsen, J.P., Voznyi, E., Norum, J., Fennelly, D., Tveit, K.M., Garin, A., Gruia, G., Mourier, A., Sibaud, D., Lefebvre, P., Beijnen, J.H., Schellens, J.H. and Bokkel-Huinink, W.W. (2004) A ran- domisedphase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectalcancer. British Journal of Cancer, 91, 1434- 1441
[7]
Fuchs, C.S., Moore, M.R., Harker, G., Villa, L., Rinaldi, D. and Hecht, J.R. (2003) Phase III comparison of two irinotecan dosing regimensin second-line therapy of me- tastatic colorectal cancer. Journal of Clinical Oncology, 21, 807-814.
[8]
Hwang, J.J., Eisenberg, S.G. and Marshall, J.L. (2003) Improving the toxicity of irinotecan/5-FU/leucovorin: A 21-day schedule. Oncology, 17, 37-43.
[9]
Fentiman, I.S., Tirelli, U., Monfardini, S., Schneider, M., Festen, J., Cognetti, F. and Aapro, M.S. (1990) Cancer in the elderly: why so badly treated. Lancet, 28, 1020-1022.
[10]
Monfardini, S. and Yancik, R. (1993) Cancer in the eld- erly: Meeting the challenge of an aging population. Jour- nal of the National Cancer Institute, 85, 532-538.
[11]
Miller, A.B., Hoogstraten, B., Staquet, M. and Winkler, A. (1981) Reporting results of cancer treatment. Cancer, 47, 207-214.
[12]
Rougier, P., Mitry, E., Cunningham, D., Roth, A., Clavero-Fabri, M.C., Magherini, E., Mery-Mignard, D., Awad, L. and Douillard, J.Y. (2003) Is age a prognostic factor of toxicity and efficacy in patients(pts) with metastatic co- lorectal cancer (MCRC) receiving irinotecan in combina- tion with 5FU/folinic acid (FA). American Society of Clinical Oncology, 22, **-**.
[13]
Chau, I., Norman, A.R., Cunningham, D., Waters, J.S., Topham, C., Middleton, G., Hill, M., Ross, P.J., Katopo- dis, R., Stewart, G. and Oates, J.R. (2004) Elderly patients with fluoropyrimidine andthymidylate synthase inhibitor- resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy. British Journal of Cancer, 91, 1453-1458.
[14]
Rothenberg, M.L., Kuhn, J.G., Burris, H.A., Nelson, J., Eckardt, J.R., Tristan-Morales, M., Hilsenbeck, S.G., Weiss, G.R., Smith, L.S. and Rodriguez, G.I. (1993) Phase I and pharmacokinetic trial of weekly CPT-11. Journal of Clinical Oncology, 11, 2194-2204.
[15]
Abigerges, D., Chabot, G.G., Armand, J.P., Herait, P., Gouyette, A. and Gandia, D. (1995) Phase I and pharma- cologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. Journal of Clinical Oncology, 13, 210-221.
[16]
Benavides, M., Garcia-Alfonso, P., Cobo, M., Munoz- Martin, A., Gil-Calle, S., Carabantes, F., Villar, E., Graupera, J., Balcells, M. and Perez-Manga, G. (2004) Weekly irinotecan (CPT-11) in 5-FU heavily pretreated and poor-performance-status patients with advanced co- lorectal cancer. Medical Oncology, 21, 255-262.
[17]
Karaoglu, A., Yalcin, S., Tekuzman, G., Kars, A., Celik, I., Guler, N., Ozisik, Y., Turker, A., Barista, I. and Gullu, I. (2003) Weekly irinotecan in patients with metastatic colorectal cancer failing 5-fluorouracil-based chemotherapy: efficacy and prognostic factors. Tumori, 89, 141-145.
[18]
Rougier, P. and Mitry, E. (2000) Colorectal cancer che- motherapy: Irinotecan. Seminars in Oncology, 27, 138- 143.
[19]
Grothey, A., Sargent, D., Goldberg, R.M. and Schmoll, H.J. (2004) Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil- leucovorin, irinotecan, and oxaliplatin in the course of treatment. Journal of Clinical Oncology, 22, 1209-1214.
[20]
Rosati, G. and Cordio, S. (2006) Single agent irinotecan as second line weekly chemotherapy in elderly patients with advanced colorectal cancer. Tumori, 92,290-294.
[21]
Tournigand, C., André, T., Achille, E., Lledo, G., Flesh, M., Mery-Mignard, D., et al. (2004) Folfiri followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. Journal of Clini- cal Oncology, 22, 229-237.
[22]
Louvet, C., André, T., Gamelin, E., Hebbar, M., Mabro, M., Bennamoun, M., Rassam, H. and De Gramont. (2010) Phase II study of biweekly pemetrexed plus irinotecan as second-line therapy for metastatic colorectal cancer. American Journal of Clinical Oncology, *, *.
[23]
Mabro, M., Artru, P., André, T., Flesch, M., Maindrault- Goebel, F., Landi, B., Lledo, G., Plantade, A., Louvet, C. and De Gramont, A. (2006) A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients. British Journal of Cancer, 94, 1287-1292.
[24]
Sorbye, H., Berglund, A., MagneTveits, K., Ogreid, D., Hoff Wandere, E., et al. (2007) Secondary treatment and predictive factors for second-line chemotherapy after first-line oxaliplatin-based therapy in metastatic colorec- tal cancer. Acta Oncologica, 46, 982-988.
[25]
Mabro, M., Artru, P., Andre, T., Flesch, M., Maindrault- Goebel, F., Landi, B., Lledo, G., Plantade, A., Louvet, C. and Gramont, A. (2006) A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU) after FOLFOX in advanced colorectal cancer patients. British Journal of Cancer, 94, 1287-1292.
[26]
Recchia, F., Nuzzo, A., Lalli, A., Di Lullo, L., De Filippis, S., Saggio, G., Di Blasio, A. and Rea, S. (2003) Multi- center phase II study of CPT-11 fractionated over two days with bimonthly leucovorin and 5-fluorouracil in pa- tients with metastatic colorectal cancer. Anti-Cancer Re- search, 23, 2903-2908.
