A phase I/II study of neoadjuvant chemotherapy with Pemetrexed (Alimta) in rectal cancer

Derwinger, Kristoffer; Kodeda, Karl; Swartling, Torbjörn; Kälebo, Peter; Carlsson, Göran; Gustavsson, Bengt

doi:10.1016/j.ejso.2011.04.003

Cited by 6 publications

(3 citation statements)

References 22 publications

(24 reference statements)

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“…The most frequent treatment-related AEs were grade 1 fatigue, nausea, and diarrhea, which are common side effects of pemetrexed therapy [ 54 ]. In contrast to previous trials of pemetrexed in patients with colorectal cancer, none of the patients in the current study reported instances of grade 3/4 neutropenia [ 39 , 40 , 55 ]. However, this was a phase 1 study, and larger phase 2/3 studies will provide a more rigorous evaluation of the safety and tolerability of [6R]-MTHF plus pemetrexed combination therapy.…”

Section: Discussioncontrasting

confidence: 97%

“…Progression-free survival in the ALIRI arm was significantly shorter than in the FOLFIRI arm (ALIRI, 5.7 months; FOLFIRI, 7.7 months; p < 0.001), and the number of drug-related deaths was higher (ALIRI, 4; FOLFIRI, 1), indicating that pemetrexed is not superior to 5-FU-based therapy in the treatment of metastatic colorectal cancer, in terms of either efficacy or safety. However, a phase 1/2 feasibility trial of preoperative pemetrexed therapy in patients with resectable rectal cancer showed a significant reduction of tumor size ( p < 0.001) and tumor-related symptoms ( p < 0.018), with a low incidence (10.8 %) of grade 3 or 4 adverse effects [ 40 ], indicating that pemetrexed is a promising treatment option in the neoadjuvant setting.…”

Section: Introductionmentioning

confidence: 99%

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Phase 1 dose de-escalation trial of the endogenous folate [6R]-5,10-methylene tetrahydrofolate in combination with fixed-dose pemetrexed as neoadjuvant therapy in patients with resectable rectal cancer

et al. 2015

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SummaryBackground Modufolin® ([6R]-5,10-methylene tetrahydrofolate; [6R]-MTHF) is an endogenous biomodulator that is being developed as an alternative to leucovorin, a folate prodrug used in the treatment of colorectal cancer. The objective of this phase 1 dose de-escalation trial was to estimate the minimum tolerated dose of [6R]-MTHF to be used in combination with pemetrexed 500 mg/m2 in the neoadjuvant treatment of patients with rectal cancer. Methods Adult patients (≥18 years) with resectable rectal adenocarcinoma were allocated to [6R]-MTHF doses of 500, 100, 50, and 10 mg/m2 in combination with pemetrexed 500 mg/m2. [6R]-MTHF was administered as an intravenous (i.v.) bolus injection 1 week prior to the first dose of pemetrexed and then once weekly for 9 weeks; pemetrexed was administered by i.v. infusion once every 21 days for three cycles. Results Twenty-four patients (mean [SD] age, 63.1 [12.9] years) were enrolled in the study. A total of 72 treatment-related adverse events (AEs) were reported, of which the most common were fatigue (n = 17; 23.6 %), nausea (n = 10; 13.9 %), and diarrhea (n = 5; 6.9 %). The incidence of treatment-related AEs by [6R]-MTHF dose level (500, 100, 50, 10 mg/m2) was 11.1 % (n = 8), 13.9 % (n = 10), 45.8 % (n = 33), and 29.2 % (n = 21), respectively. There were no dose-limiting toxicities, and only two (2.8 %) treatment-related AEs were grade 3 in severity. Of the 11 serious AEs reported, none were considered to be related to [6R]-MTHF treatment. Conclusions The results of this phase 1 study indicate that the estimated minimum tolerated dose of [6R]-MTHF was 100 mg/m2 once weekly in combination with pemetrexed 500 mg/m2. The low toxicity profile of [6R]-MTHF supports its further evaluation as a component of systemic chemotherapy in the management of colon and rectal cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s10637-015-0272-0) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Phase 1 dose de-escalation trial of the endogenous folate [6R]-5,10-methylene tetrahydrofolate in combination with fixed-dose pemetrexed as neoadjuvant therapy in patients with resectable rectal cancer

et al. 2015

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“…An important attribute of pemetrexed is the lower toxicities and relative high efficacy (Calvert AH et al, 2004). Recent study reported that pemetrexed alone in neoadjuvant chemotherapy of rectal cancer had a better objective response rate and disease control rate (Derwinger K et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

A Predictive Model for Evaluating Responsiveness to Pemetrexed Treatment in Patients with Advanced Colorectal Cancer

Wu¹,

Huang²,

Cao³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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. Nevertheless, many patients still failed to treatment due to tumor recurrence and metastasis, and 5-year survival rate still less than 10%.Pemetrexed is a new anticancer drug. 2 by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected.We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.

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Effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells

Zhang

Xie

Liu

et al. 2013

Cancer Chemother Pharmacol

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A phase I/II study of neoadjuvant chemotherapy with Pemetrexed (Alimta) in rectal cancer

Cited by 6 publications

References 22 publications

Phase 1 dose de-escalation trial of the endogenous folate [6R]-5,10-methylene tetrahydrofolate in combination with fixed-dose pemetrexed as neoadjuvant therapy in patients with resectable rectal cancer

Phase 1 dose de-escalation trial of the endogenous folate [6R]-5,10-methylene tetrahydrofolate in combination with fixed-dose pemetrexed as neoadjuvant therapy in patients with resectable rectal cancer

A Predictive Model for Evaluating Responsiveness to Pemetrexed Treatment in Patients with Advanced Colorectal Cancer

Effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells

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