A Randomized, Double-Blind, Phase II Study of Two Doses of Pemetrexed as First-Line Chemotherapy for Advanced Breast Cancer

Llombart-Cussac, Antonio; Martín, Miguel; Harbeck, Nadia; Anghel, Rodica; Eniu, Alex; Verrill, M.; Neven, Patrick; Grève, Jacques De; Melemed, Allen S.; Clark, Romnee; Simms, Lorinda; Kaiser, Christopher J.; Ma, Doreen

doi:10.1158/1078-0432.ccr-06-2377

Cited by 27 publications

(15 citation statements)

References 31 publications

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“…Another patient who received 900 mg/m 2 developed renal failure that resolved 13 days after cessation of the drug. 6 In another phase III trial, in 121 fully vitaminsupplemented patients who received pemetrexed (500 mg/m 2 ), 2 patients experienced grade 1 and 2 (reversible) decrease in creatinine clearance. 7 Since most of the trials had excluded patients with baseline creatinine clearance of <60 mL/min because of increased toxicity, little is known about the potential nephrotoxic effects of pemetrexed at a lower level of renal function.…”

Section: Discussionmentioning

confidence: 99%

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

et al. 2010

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We present a case of interstitial nephritis and nephrogenic diabetes insipidus (NDI) in a patient treated with pemetrexed (500 mg/m 2 ) for non-small cell lung cancer. Renal impairment and diabetes insipidus appeared after the first treatment cycle while he totally received four cycles of chemotherapy. There was not any significant myelosuppression and the patient was on regular supplementation with folic acid and vitamin B 12 . He was not on any other medications and he did not receive any nephrotoxic agents. Kidney biopsy showed acute tubular necrosis together with interstitial inflammatory infiltrate of mononuclear cells and interstitial fibrosis occupying 25% of the cortex. There was not any improvement of renal function after a 2-week trial of oral prednisone. In the present case report, we review the literature for pemetrexed-induced renal toxicity and the possible mechanisms involved.

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Section: Discussionmentioning

confidence: 99%

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

et al. 2010

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“…In our study of dose-dense, single-agent pemetrexed given as first-line treatment to women with MBC, we observed an ORR of 26% (CR 3%, PR 23%) and 40% CBR. Llombart-Cussac and colleagues observed response rates of 17 and 19% when pemetrexed was given at 600 and 900 mg/m 2 to MBC patients in the first-line setting on Day 1 of a 21-day cycle [25]. Earlier 21-day trials have shown response rates in anthracyclinerefractory groups (ORR 17%), anthracycline-failure groups (ORR 24%), anthracycline-and taxane-pretreated groups (ORR 26% and ORR 28%, respectively), and heavily pretreated groups who had received prior anthracycline, a taxane, and capecitabine (ORR 8%) [15,17,26].…”

Section: Discussionmentioning

confidence: 99%

Results of a phase II study of pemetrexed as first-line chemotherapy in patients with advanced or metastatic breast cancer

Robert

Conkling

O’Rourke

et al. 2010

Breast Cancer Res Treat

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Palliation is the primary goal in metastatic breast cancer (MBC), and safe, efficacious, new single-agent options are needed. Pemetrexed, an antifolate, inhibits several folate-dependent enzymes involved in purine biosynthesis. The primary goal of this study was to determine the objective response rate in patients with advanced or MBC given pemetrexed as a first-line, dose-dense, every 2-week chemotherapy. Women with HER2-negative advanced or MBC, without prior cytotoxic treatment for this stage of disease, were treated with intravenous pemetrexed 600 mg/m² on Day 1 of each 14-day cycle. Standard dexamethasone, folic acid, and vitamin B(12) premedications were given. 37 patients enrolled; 36 received ≥ 1 dose of pemetrexed and 35 were evaluable for response. Median age of patients was 61.4 years, 76% were hormone receptor positive (ER+ and/or PR+). Prior treatment included adjuvant chemotherapy (57%) and/or endocrine (65%). Patients received a median of 6 cycles of pemetrexed (range, 1-21). Based on 35 evaluable patients, the overall response rate (ORR) was 26% (1 CR and 8 PR), and the clinical benefit rate (CR+ PR+ stable disease [SD] ≥ 6 months) was 40%. Median progression-free survival (PFS) was 4.1 months (range, <1-22.4). Median overall survival (OS) was 18.9 months (range, <1-27.7). Grades 3-4 treatment-related toxicities included: neutropenia (36%), leukopenia (17%), fatigue (14%), and anemia (14%). Grade 1/2 alopecia was seen in 8% of patients. This phase II study of dose-dense, single-agent pemetrexed showed moderate activity in the first-line setting with acceptable toxicity and no significant alopecia.

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“…In a phase II trial where advanced metastatic breast cancer patients received 600 or 900 mg/m 2 pemetrexed as a first-line treatment, pemetrexed produced moderate antitumor activity, with response rate at 16% and a clinical benefit at approximately 40% [16]. In two phase II studies, where advanced colorectal cancer patients received pemetrexed at 600 or 500 mg/m 2 as firstline treatment, objective response rates were 15.4% and 17.2%, respectively [17].…”

Section: Discussionmentioning

confidence: 99%

A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma

Cohn¹,

Myers²,

Mamus³

et al. 2008

Invest New Drugs

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Pemetrexed has demonstrated activity in hepatocellular carcinoma (HCC) cell lines, and has a manageable toxicity profile in clinical trials, suggesting its potential as a treatment for HCC patients. A multicenter, Phase II community-based study was conducted to assess the response rate and toxicity profile of single-agent pemetrexed in first-line patients with advanced or metastatic HCC. Patients premedicated with folic acid, vitamin B(12), and dexamethasone were administered pemetrexed 600 mg/m(2) IV on day 1 of each 21-day cycle until disease progression. This nonrandomized study employed Simon's 2-stage design, enrolling 21 eligible patients in the first stage, stopping accrual if < or =2 responders were observed. Responses were four stable disease, 14 progressive disease, and three not evaluable: two had early toxicities (renal/liver failure, sepsis) and one was noncompliant. The most common grade 3 hematological toxicities were neutropenia 6 of 21 (29%) and thrombocytopenia 3 of 21 (14%); with no grade 4 toxicities. Thirteen patients died on-study: 12 PD and one liver failure; none were drug-related. The median survival was 5.2 months (range, <1-12.2). The planned second stage was cancelled, and the trial was closed owing to lack of response. While pemetrexed was tolerated in this patient population, it was not active.

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A Randomized, Double-Blind, Phase II Study of Two Doses of Pemetrexed as First-Line Chemotherapy for Advanced Breast Cancer

Cited by 27 publications

References 31 publications

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

Interstitial nephritis and nephrogenic diabetes insipidus in a patient treated with pemetrexed

Results of a phase II study of pemetrexed as first-line chemotherapy in patients with advanced or metastatic breast cancer

A phase II study of pemetrexed in patients with advanced hepatocellular carcinoma

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