Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 3/2015

01.03.2015 | Original Article

A phase II study of capecitabine and oral leucovorin as a third-line chemotherapy in patients with metastatic colorectal cancer

verfasst von: Dae Ro Choi, Sang Nam Yoon, Hyeong Su Kim, Jung Han Kim, Kwang Yong Kim, Byung Chun Kim, Young Kyun Choi, Jin Bae Kim, Boram Han, Hun Ho Song, Dae Young Zang

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

This study was conducted to evaluate the efficacy and safety of the combination of capecitabine and oral leucovorin (LV) as a third-line chemotherapy for patients with metastatic colorectal cancer (CRC) showing resistance to irinotecan- and oxaliplatin-containing regimens.

Method

Patients who showed disease progression while receiving or within 6 months of discontinuing irinotecan- and oxaliplatin-containing regimens received capecitabine 825 mg/m2 in combination with oral LV at a fixed dose of 30 mg, twice a day for 2 weeks followed by a 1-week rest.

Results

Twenty-five patients were enrolled from July 2011 to June 2014. Three patients achieved PR, and 11 showed SD. The overall response rate was 12 %, and disease control rate was 56 %. With a median follow-up of 6.8 months, the median time to progression was 2.8 months and the median overall survival was 7.1 months. The most common non-hematologic toxicity was hand-foot syndrome (40 %), followed by mucositis (28 %) and diarrhea (12 %). Grade 3 hand-foot syndrome occurred in two patients (8 %), and grade 3 mucositis in one. Hematologic toxicities were mild, and only one patient developed grade 3 thrombocytopenia.

Conclusion

The combination of capecitabine and oral LV showed a modest activity and tolerable toxicity profile in metastatic CRC patients pretreated with irinotecan- and oxaliplatin-containing regimens. Oral LV seems to be able to reduce the usual dose of capecitabine when the two drugs are combined.
Literatur
1.
Zurück zum Zitat Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. doi:10.1002/ijc.29210 CrossRefPubMed Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. doi:10.​1002/​ijc.​29210 CrossRefPubMed
3.
Zurück zum Zitat Thrion P, Michiels S, Pignon JP, Buyse M, Braud AC, Carlson RW, O’Connell M, Sargent P, Piedbois P, Meta-Analysis Group in Cancer (2004) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis. J Clin Oncol 22(18):3766–3775. doi:10.1200/JCO.2004.03.104 CrossRef Thrion P, Michiels S, Pignon JP, Buyse M, Braud AC, Carlson RW, O’Connell M, Sargent P, Piedbois P, Meta-Analysis Group in Cancer (2004) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis. J Clin Oncol 22(18):3766–3775. doi:10.​1200/​JCO.​2004.​03.​104 CrossRef
4.
Zurück zum Zitat de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18(16):2938–2947PubMed de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18(16):2938–2947PubMed
5.
Zurück zum Zitat Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Le Rol A, Walter S, Adam R, Misset JL, Lévi F (2000) Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 18(1):136–147PubMed Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Le Rol A, Walter S, Adam R, Misset JL, Lévi F (2000) Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 18(1):136–147PubMed
6.
Zurück zum Zitat Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355(9209):1041–1047. doi:10.1016/S0140-6736(00)02034-1 CrossRefPubMed Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355(9209):1041–1047. doi:10.​1016/​S0140-6736(00)02034-1 CrossRefPubMed
7.
Zurück zum Zitat Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H (1998) Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 34(8):1274–1281. doi:10.1016/S0959-8049(98)00058-6 CrossRefPubMed Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H (1998) Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 34(8):1274–1281. doi:10.​1016/​S0959-8049(98)00058-6 CrossRefPubMed
8.
Zurück zum Zitat Ishikawa T, Sekiguchi F, Fukase Y, Sawada N, Ishitsuka H (1998) Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res 58(4):685–690PubMed Ishikawa T, Sekiguchi F, Fukase Y, Sawada N, Ishitsuka H (1998) Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res 58(4):685–690PubMed
9.
Zurück zum Zitat Cao S, Lu K, Ishitsuka H, Rustum YM (1997) Anti-tumor efficacy of capecitabine against fluorouracil-sensitive and—resistant tumors. Proc Am Soc Clin Oncol 16:226a (abstr 795) Cao S, Lu K, Ishitsuka H, Rustum YM (1997) Anti-tumor efficacy of capecitabine against fluorouracil-sensitive and—resistant tumors. Proc Am Soc Clin Oncol 16:226a (abstr 795)
10.
Zurück zum Zitat Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P, Xeloda Colorectal Cancer Study Group (2001) Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19(21):4097–4106PubMed Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P, Xeloda Colorectal Cancer Study Group (2001) Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19(21):4097–4106PubMed
11.
Zurück zum Zitat Cassidy J, Twelves C, Van cutsem E, Hoff P, Bajetta E, Boyer M, Bugat R, Burger U, Garin A, Graeven U, McKendric J, Maroun J, Marshall J, Osterwalder B, Pérez-Manga G, Rosso R, Rougier P, Schilsky RL, Capecitabine Colorectal Cancer Study Group (2002) First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol 13(4):566–575. doi:10.1093/annonc/mdf089 CrossRefPubMed Cassidy J, Twelves C, Van cutsem E, Hoff P, Bajetta E, Boyer M, Bugat R, Burger U, Garin A, Graeven U, McKendric J, Maroun J, Marshall J, Osterwalder B, Pérez-Manga G, Rosso R, Rougier P, Schilsky RL, Capecitabine Colorectal Cancer Study Group (2002) First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol 13(4):566–575. doi:10.​1093/​annonc/​mdf089 CrossRefPubMed
12.
Zurück zum Zitat Kim ST, Choi YJ, Park KH, Oh SC, Seo JH, Shin SW, Kim JS, Kim YH (2011) Capecitabine monotherapy as salvage treatment after failure of chemotherapy containing oxaliplatin and irinotecan in patients with metastatic colorectal cancer. Asia Pac J Clin Oncol 7(1):82–87. doi:10.1111/j.1743-7563.2010.01363.x CrossRefPubMed Kim ST, Choi YJ, Park KH, Oh SC, Seo JH, Shin SW, Kim JS, Kim YH (2011) Capecitabine monotherapy as salvage treatment after failure of chemotherapy containing oxaliplatin and irinotecan in patients with metastatic colorectal cancer. Asia Pac J Clin Oncol 7(1):82–87. doi:10.​1111/​j.​1743-7563.​2010.​01363.​x CrossRefPubMed
13.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216. doi:10.1093/jnci/92.3.205 CrossRefPubMed Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216. doi:10.​1093/​jnci/​92.​3.​205 CrossRefPubMed
14.
Zurück zum Zitat Cassidy J, Dirix L, Bissett D, Reigner B, Griffin T, Allman D, Osterwalder B, Van Oosterom AT (1998) A phase I study of capecitabine in combination with oral leucovorin in patients with intractable solid tumors. Clin Cancer Res 4(11):2755–2761PubMed Cassidy J, Dirix L, Bissett D, Reigner B, Griffin T, Allman D, Osterwalder B, Van Oosterom AT (1998) A phase I study of capecitabine in combination with oral leucovorin in patients with intractable solid tumors. Clin Cancer Res 4(11):2755–2761PubMed
16.
Zurück zum Zitat Van Cutsem E, Findlay M, Osterwalder B, Kocha W, Dalley D, Pazdur R, Cassidy J, Dirix L, Twelves C, Allman D, Seitz JF, Schölmerich J, Burger HU, Verweij J (2000) Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized phase II study. J Clin Oncol 18(6):1337–1345PubMed Van Cutsem E, Findlay M, Osterwalder B, Kocha W, Dalley D, Pazdur R, Cassidy J, Dirix L, Twelves C, Allman D, Seitz JF, Schölmerich J, Burger HU, Verweij J (2000) Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized phase II study. J Clin Oncol 18(6):1337–1345PubMed
Metadaten
Titel
A phase II study of capecitabine and oral leucovorin as a third-line chemotherapy in patients with metastatic colorectal cancer
verfasst von
Dae Ro Choi
Sang Nam Yoon
Hyeong Su Kim
Jung Han Kim
Kwang Yong Kim
Byung Chun Kim
Young Kyun Choi
Jin Bae Kim
Boram Han
Hun Ho Song
Dae Young Zang
Publikationsdatum
01.03.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 3/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2688-9

Weitere Artikel der Ausgabe 3/2015

Cancer Chemotherapy and Pharmacology 3/2015 Zur Ausgabe

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.