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Gemcitabine plus capecitabine (Gem-Cape) biweekly in chemorefractory metastatic colorectal cancer.

Jiménez-Fonseca P, Solis MP, Garrido M, Faez L, Rodriguez D, Ruiz AL, Sanchez Lorenzo ML, Uriol E, Menendez MD, Viéitez JM - Clin Transl Oncol (2014)

Bottom Line: Objective response rates and stable disease rates at 3 months were 6.72 and 37.81 %, equalling a clinical benefit of 44.53 %.Statistical significance was obtained by subgroups, assessing clinical benefits and objective responses for PFS and OS.These data suggest that Gem-Cape is a tolerable and feasible regimen, associated with clinical benefit in non-selected, heavily pretreated, mCRC patients.

View Article: PubMed Central - PubMed

Affiliation: Medical Oncology Department, Asturias Central University Hospital, Carretera de Rubín s/n Finca "La Cadellada", 33011, Oviedo, Asturias, Spain, palucaji@hotmail.com.

ABSTRACT

Purpose: A proportion of patients with metastatic colorectal cancer (mCRC) are still able to continue with active therapy after their progression to fluoropyrimidines, oxaliplatin, and irinotecan regimens. Studies suggest that gemcitabine and fluoropyrimidines are synergic antimetabolites. The purpose was to evaluate gemcitabine-capecitabine (Gem-Cape) in heavily pretreated mCRC and to thus assess possible predictive factors for progression-free survival (PFS) and overall survival (OS).

Patients and methods: This analysis was performed on 119 evaluable patients pretreated with fluoropyrimidines, oxaliplatin, irinotecan, and biological agents between June 2001 and July 2011. Patients received gemcitabine 1,000 mg/m(2) day 1 and capecitabine 1,000 mg/m(2) bid for 7 days every 2 weeks.

Results: The general characteristics were ECOG 0-1, 89 %; male, 68 %, and median age 63 years. In total, 61 % had received two chemotherapy lines, while 39 % had received three or more. Objective response rates and stable disease rates at 3 months were 6.72 and 37.81 %, equalling a clinical benefit of 44.53 %. The median PFS and OS were 2.87 months [95 % confidence interval (CI) 2.53-3.17 months] and 6.53 months (95 % CI 5.33-8.77), respectively. The most frequent toxicities were grades 1-2, anemia (22 %), thrombocytopenia (10 %), and hand-foot syndrome (9 %); grade ≥3, diarrhea (2 %), with no treatment-related discontinuations. No treatment-related deaths were reported. Statistical significance was obtained by subgroups, assessing clinical benefits and objective responses for PFS and OS. Moreover, patients under 65 tended to have a better PFS.

Conclusion: These data suggest that Gem-Cape is a tolerable and feasible regimen, associated with clinical benefit in non-selected, heavily pretreated, mCRC patients.

No MeSH data available.


Related in: MedlinePlus

Interaction and synergism involving fluoropyrimidines and gemcitabine. Yellow triangles signal the active metabolites of this synergistic combination able to produce direct damage to nucleic acids. The blue pathway refers to normal integration of pyrimidines into DNA and RNA. The purple line represents fluoropyrimidines metabolism, just as the green pathway depicts to gemcitabine intervention. Crossroad and so synergism is located at tymidylate synthase (TS), being inhibited directly by fluoropyrimidine metabolite FdUDP and indirectly by the inhibition of the enzyme that catalyzes TS substratum, dUMP (deoxiuridine monophosphate)
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Related In: Results  -  Collection


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Fig1: Interaction and synergism involving fluoropyrimidines and gemcitabine. Yellow triangles signal the active metabolites of this synergistic combination able to produce direct damage to nucleic acids. The blue pathway refers to normal integration of pyrimidines into DNA and RNA. The purple line represents fluoropyrimidines metabolism, just as the green pathway depicts to gemcitabine intervention. Crossroad and so synergism is located at tymidylate synthase (TS), being inhibited directly by fluoropyrimidine metabolite FdUDP and indirectly by the inhibition of the enzyme that catalyzes TS substratum, dUMP (deoxiuridine monophosphate)

Mentions: Capecitabine, another antimetabolite, is an inactive prodrug that undergoes a complex process to reach its active form. Capecitabine conversion to 5-fluorouracil (5-FU) is higher in tumor cells than in normal tissues because of the higher expression of thymidine phosphorylase [5]. The depletion of the reduced nucleotide pool could increase the incorporation of the 5-FU metabolite fluorouridine monophosphate (FUTP) into RNA and of FdUTP into DNA, resulting in damaged RNA and DNA synthesis and function [6] (Fig. 1).Fig. 1


Gemcitabine plus capecitabine (Gem-Cape) biweekly in chemorefractory metastatic colorectal cancer.

Jiménez-Fonseca P, Solis MP, Garrido M, Faez L, Rodriguez D, Ruiz AL, Sanchez Lorenzo ML, Uriol E, Menendez MD, Viéitez JM - Clin Transl Oncol (2014)

Interaction and synergism involving fluoropyrimidines and gemcitabine. Yellow triangles signal the active metabolites of this synergistic combination able to produce direct damage to nucleic acids. The blue pathway refers to normal integration of pyrimidines into DNA and RNA. The purple line represents fluoropyrimidines metabolism, just as the green pathway depicts to gemcitabine intervention. Crossroad and so synergism is located at tymidylate synthase (TS), being inhibited directly by fluoropyrimidine metabolite FdUDP and indirectly by the inhibition of the enzyme that catalyzes TS substratum, dUMP (deoxiuridine monophosphate)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4544491&req=5

Fig1: Interaction and synergism involving fluoropyrimidines and gemcitabine. Yellow triangles signal the active metabolites of this synergistic combination able to produce direct damage to nucleic acids. The blue pathway refers to normal integration of pyrimidines into DNA and RNA. The purple line represents fluoropyrimidines metabolism, just as the green pathway depicts to gemcitabine intervention. Crossroad and so synergism is located at tymidylate synthase (TS), being inhibited directly by fluoropyrimidine metabolite FdUDP and indirectly by the inhibition of the enzyme that catalyzes TS substratum, dUMP (deoxiuridine monophosphate)
Mentions: Capecitabine, another antimetabolite, is an inactive prodrug that undergoes a complex process to reach its active form. Capecitabine conversion to 5-fluorouracil (5-FU) is higher in tumor cells than in normal tissues because of the higher expression of thymidine phosphorylase [5]. The depletion of the reduced nucleotide pool could increase the incorporation of the 5-FU metabolite fluorouridine monophosphate (FUTP) into RNA and of FdUTP into DNA, resulting in damaged RNA and DNA synthesis and function [6] (Fig. 1).Fig. 1

Bottom Line: Objective response rates and stable disease rates at 3 months were 6.72 and 37.81 %, equalling a clinical benefit of 44.53 %.Statistical significance was obtained by subgroups, assessing clinical benefits and objective responses for PFS and OS.These data suggest that Gem-Cape is a tolerable and feasible regimen, associated with clinical benefit in non-selected, heavily pretreated, mCRC patients.

View Article: PubMed Central - PubMed

Affiliation: Medical Oncology Department, Asturias Central University Hospital, Carretera de Rubín s/n Finca "La Cadellada", 33011, Oviedo, Asturias, Spain, palucaji@hotmail.com.

ABSTRACT

Purpose: A proportion of patients with metastatic colorectal cancer (mCRC) are still able to continue with active therapy after their progression to fluoropyrimidines, oxaliplatin, and irinotecan regimens. Studies suggest that gemcitabine and fluoropyrimidines are synergic antimetabolites. The purpose was to evaluate gemcitabine-capecitabine (Gem-Cape) in heavily pretreated mCRC and to thus assess possible predictive factors for progression-free survival (PFS) and overall survival (OS).

Patients and methods: This analysis was performed on 119 evaluable patients pretreated with fluoropyrimidines, oxaliplatin, irinotecan, and biological agents between June 2001 and July 2011. Patients received gemcitabine 1,000 mg/m(2) day 1 and capecitabine 1,000 mg/m(2) bid for 7 days every 2 weeks.

Results: The general characteristics were ECOG 0-1, 89 %; male, 68 %, and median age 63 years. In total, 61 % had received two chemotherapy lines, while 39 % had received three or more. Objective response rates and stable disease rates at 3 months were 6.72 and 37.81 %, equalling a clinical benefit of 44.53 %. The median PFS and OS were 2.87 months [95 % confidence interval (CI) 2.53-3.17 months] and 6.53 months (95 % CI 5.33-8.77), respectively. The most frequent toxicities were grades 1-2, anemia (22 %), thrombocytopenia (10 %), and hand-foot syndrome (9 %); grade ≥3, diarrhea (2 %), with no treatment-related discontinuations. No treatment-related deaths were reported. Statistical significance was obtained by subgroups, assessing clinical benefits and objective responses for PFS and OS. Moreover, patients under 65 tended to have a better PFS.

Conclusion: These data suggest that Gem-Cape is a tolerable and feasible regimen, associated with clinical benefit in non-selected, heavily pretreated, mCRC patients.

No MeSH data available.


Related in: MedlinePlus