Oral piritrexim, an effective treatment for metastatic urothelial cancer

Wit, Ronald de; Kaye, SB; Roberts, JT; Stoter, G.; Scott, J; Verweij, Jaco J.

doi:10.1038/bjc.1993.71

Cited by 52 publications

(11 citation statements)

References 14 publications

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“…In a phase II study of 31 patients with melanoma a 23% response rate was reported for the single agent [148], and yet in combination with DTIC, no responses were observed in 17 evaluable patients [149]. Initial observations suggested intriguing activity in bladder cancer: in a second line setting there were 3 PRs in 13 evaluable patients (23% RR) [139], and in a study of 33 chemotherapy naive patients there was a complete response lasting 19+ weeks, and 10 PRs for an overall response rate of 38% in 29 evaluable patients [140]. Three of four patients with bladder cancer who progressed following MVAC had a partial response to treatment with oral piritrexim [150].…”

Section: Piritreximmentioning

confidence: 94%

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

2006

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Section: Piritreximmentioning

confidence: 94%

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

2006

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“…There is a limited number of phase II studies employing repeated daily dosing with oral PTX. These studies showed tumour responses in seven out of 31 patients with metastatic melanoma, one out of 31 non-small cell lung carcinoma patients, in 11 out of 29 patients with metastatic urothelial cancer, and nine of 33 with advanced head and neck cancer (Feun et al, 1991;Kris et al, 1987;De Wit et al, 1993;Uen et al, 1992). These data suggest that for melanoma and urothelial cancer PTX might be superior to that of the mother compound methotrexate.…”

Section: Discussionmentioning

confidence: 76%

“…Tumour responses have been observed in phase II studies in melanoma, non-small cell lung carcinoma, bladder carcinoma, and head and neck cancer (Feun et al, 1991;Kris et al, 1987;De Wit et al, 1993;Uen et al, 1992).…”

Section: Piritreximmentioning

confidence: 99%

A phase II and pharmacokinetic study with oral piritrexim for metastatic breast cancer

Vries

Gietema²,

Workman³

et al. 1993

Br J Cancer

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Piritrexim is a lipid-soluble antifolate which, like methotrexate, has a potent capacity to inhibit dihydrofolate reductase. We performed a multicentre phase II study with piritrexim in patients with locally advanced or metastatic breast cancer. Twenty-four patients of which sixteen had received prior chemotherapy, were initially treated with 25 mg piritrexim orally administered trice daily for four days, repeated weekly, with provision for dose escalation or reduction according to observed toxicity. Of twenty-one patients evaluable for tumour response, one patient achieved a partial response which lasted for 24 weeks. Three patients had stable disease during 12 weeks of treatment, seventeen had progressive disease. Pirtrexim was generally well tolerated, in eighteen patients the dose could be escalated. Myelotoxicity was the most frequent observed toxicity of this piritrexim regimen. Leucopenia and thrombocytopenia grade 3/4 occurred in 38% of the patients sometime during treatment. Pharmacokinetic analysis of piritrexim in three patients during the first treatment cycle, revealed peak levels 1 to 2 h after an oral dose, with a trend towards a higher peak plasma levels and AUCs on the fourth dosing day compared with the first dosing day. In conclusion, orally administered piritrexim appears to be a regimen with little activity in patients with locally advanced or metastatic breast carcinoma.

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“…7 In a study on chemotherapy-naive patients with advanced urothelial cancer, PTX was observed to have an overall response rate of 38%. 8 In a report by Feun et al, 9 three of four patients with methotrexate, vinblastine, doxorubicin, cisplatin refractory bladder cancers responded to treatment with piritrexim. Other cancers have also shown responses to piritrexim in early clinical studies, namely, advanced head/neck cancers, 10 sarcomas, 11 and melanoma.…”

mentioning

confidence: 98%

Gemcitabine, Paclitaxel, and Piritrexim

Liu¹,

Bailey²,

Arzoomanian³

et al. 2003

American Journal of Clinical Oncology

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Piritrexim is a new antifolate that has shown activity in methotrexate-resistant tumors. Gemcitabine is an antimetabolite similar in structure to cytosine arabinoside with early studies demonstrating activity in a variety of cancers. It also has apparent synergistic activity with antifolates from initial work in tumor models. Paclitaxel is an antimicrotubule agent that has a wide spectrum of activity against a variety of solid tumors. The combination of gemcitabine, paclitaxel, and piritrexim was assessed in this phase I trial. Thirty patients were enrolled. The starting doses were piritrexim 25 mg orally twice daily (days 1-4, 15-18), paclitaxel 75 mg/m2 (days 1, 15), and gemcitabine 750 mg/m2 (days 1, 15), which then was escalated in a stepwise fashion. Four patients achieved stable disease while on study, whereas one patient with a poorly differentiated neuroendocrine tumor achieved a partial response. The main toxicity was myelosuppression. The maximum tolerated dose was thought to be piritrexim 25 mg orally three times daily (days 1-4), paclitaxel 150 to 175 mg/m2 (days 1, 15), and gemcitabine 1,000 mg/m2 (days 1, 15). The combination of these new antifolates with paclitaxel and gemcitabine appears safe and should be considered for phase II trials in known responsive tumors such as transitional cell carcinomas.

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Oral piritrexim, an effective treatment for metastatic urothelial cancer

Cited by 52 publications

References 14 publications

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

A phase II and pharmacokinetic study with oral piritrexim for metastatic breast cancer

Gemcitabine, Paclitaxel, and Piritrexim

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