Phase II Open-Label Study of Oral Piritrexim in Patients with Advanced Carcinoma of the Urothelium Who Have Experienced Failure with Standard Chemotherapy

Lassiter, Lance K.; Tummala, Mohan K.; Hussain, Maha; Stadler, Walter M.; Petrylak, Daniel P.; Carducci, Michael A.

doi:10.3816/cgc.2008.n.005

Cited by 13 publications

(7 citation statements)

References 27 publications

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“…Those results have been further confirmed by another phase ii trial in 23 previously treated patients, among e28 whom only 2 demonstrated stable disease after 2-4 cycles; further enrolment was therefore halted 69 . Another anti-folate, pemetrexed, was investigated in a phase ii trial in 47 patients who had a performance status of 0 or 1 and adequate organ function, and who had been treated with one prior chemotherapy regimen 59 .…”

Section: Single-agent Second-line Therapysupporting

confidence: 59%

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

2011

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but little improvement has been achieved in the outcomes of patients with advanced or metastatic disease. Almost 90% of those patients eventually succumb to their cancer.For patients who relapse after first-line chemotherapy, the prognosis is generally poor. To date, there is no real consensus on how to best treat these patients, and most of the available evidence stems from small phase ii trials that have mostly failed to show survival benefit over supportive care. The present review provides an update on the management of metastatic bc, with a focus on first-line and secondline therapies. FIRST-LINE THERAPY Single-Agent TherapySingle-agent therapy has generally failed to provide adequate results in patients with advanced bc. In a phase iii trial of patients randomized to receive either cisplatin alone or in combination [methotrexate, vinblastine, doxorubicin, and cisplatin (mvac)], the overall response rate (or) was only 12% in the cisplatin arm, with only 4 of 122 patients (3.3%) remaining alive at 3 years of follow-up 4 . Similar results were observed in phase ii trials with carboplatin [or: 18%; median duration of survival (mds): 16 months] 5 . In a phase iii trial examining the role of lobaplatin, 2 of 17 patients (12%) achieved a partial response (pr), but the study was terminated because of high toxicity rates 6 . Other drugs investigated in phase ii trials have manifested variable activity against advanced urothelial cancer: oral piritrexim (or: 23%; mds: 22 weeks) 7 , trimetrexate (or: 17%; mds not reported) 8 , and docetaxel (or: 13%; mds: 9 months) 9 . However, some improved results were obtained with other single agents such as paclitaxel and gemcitabine 10,11 . In a phase ii trial of 26 patients with advanced bc treated with paclitaxel, the or was 42%, and the mds, 8.4 months 10 . Similarly, in a phase ii trial of gemcitabine in 40 patients, an or of 28% was reported, with a mds of 54 weeks 11 . ABSTRACTUrothelial cancer of the bladder is the 4th most common malignancy in American men and the 9th most common in women. Although it is a chemosensitive disease, advanced bladder cancer seems to have reached a plateau with regard to median survival of patients. Standard first-line therapy remains gemcitabine plus cisplatin (gc) or methotrexate, vinblastine, doxorubicin, and cisplatin (mvac). In patients deemed unfit to receive cisplatin, gemcitabine plus carboplatin or gemcitabine plus paclitaxel can be considered. To date, no standard therapy has been established for patients who recur or are refractory to first-line therapy. Second-line vinflunine, by way of superiority over best supportive care, has shown promise in a phase iii trial. Cisplatin-based therapy (mvac or gc) can also be offered to patients previously treated with cisplatin, especially if they responded previously and are considered platinum-sensitive. Novel targeted therapies are sorely needed to further improve the delivery and efficacy of chemotherapy.

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Section: Single-agent Second-line Therapysupporting

confidence: 59%

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

2011

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“…More importantly, the clinical relevance of this treatment has been limited by the emergence of GC as a new standard, as many of the patients on progression will have been exposed to gemcitabine. Equally modest activity has been reported with novel agents, such as pemetrexed, piritrexim, and vinflunine 12,13,20–22. Therefore, there is a need for more effective treatment in relapsed advanced urothelial cancer.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of methotrexate/vinblastine/doxorubicin/cisplatin combination in gemcitabine-pretreated patients with advanced urothelial cancer: a retrospective analysis

Karadimou

Lianos²,

Pectasides³

et al. 2010

OAJU

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ObjectiveSecond-line treatment options in advanced urothelial cancer are limited. We investigated the efficacy of a methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) combination after failure of gemcitabine/platinum chemotherapy.Patients and methodsTwenty-five patients with advanced urothelial cancer, who received second-line MVAC after first-line gemcitabine/cisplatin (n = 9) or gemcitabine/carboplatin (n = 16), were included in this retrospective analysis.ResultsTwenty-two patients (88%) relapsed within 6 months after first-line treatment. Following MVAC, there were 5 (20%) objective responses. Median follow-up was 20.2 months. Median progression-free survival (PFS) was 3.8 months (95% CI: 2.3–5.2), and median overall survival (OS) was 9 months (95% CI: 6.6–11.4). Eastern Cooperative Oncology Group performance status 0.1 versus 2 was associated with longer PFS (5 months versus 3.3 months, P = 0.049). Response or stabilization of disease during second-line chemotherapy predicted for a significantly longer PFS and OS (7.4 versus 3.5, P = 0.005; 15.5 versus 7, P = 0.046).ConclusionsSecond-line MVAC chemotherapy may result in prolonged survival in some patients with refractory disease. Further research in this field is necessary.

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“…67 Piritrexim has been assayed for the treatment of psoriasis, pneumonia, and several cancers, including phase II studies for the treatment of advanced carcinoma of the urotelium. 68 …”

Section: Nonclassical (Lipophilic) Dhfr Inhibitorsmentioning

confidence: 97%

Antimetabolites That Interfere with Nucleic Acid Biosynthesis

Avendaño

Menéndez

2015

Medicinal Chemistry of Anticancer Drugs

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Phase II Open-Label Study of Oral Piritrexim in Patients with Advanced Carcinoma of the Urothelium Who Have Experienced Failure with Standard Chemotherapy

Cited by 13 publications

References 27 publications

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

Efficacy of methotrexate/vinblastine/doxorubicin/cisplatin combination in gemcitabine-pretreated patients with advanced urothelial cancer: a retrospective analysis

Antimetabolites That Interfere with Nucleic Acid Biosynthesis

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