Hexamethylmelamine, methotrexate, 5-fluorouracil as second line chemotherapy after platinum for epithelial ovarian malignancies

Belinson, Jerome L.; Pretorius, R G; McClure, Maura; Ashikaga, Takamaru

doi:10.1016/0090-8258(86)90130-7

Cited by 7 publications

(1 citation statement)

References 13 publications

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“…However, when the disease is primarily resistant, or when relapse occurs within a year, the prospects for second-line treatment are bleak. Phase II studies in this situation, either with single agents (Sutton et al, 1989;Coleman et al, 1989;1990;Manetta et al, 1990) or with combination chemotherapy (Belinson et al, 1986;Benedetti-Panici et al, 1990;Pater et al, 1987), have generally yielded few responses, of short duration. Even the promising new agent, taxol, gives responses in only 20-30% of this group of patients (Einzig et al, 1992;McGuire et al, 1989;Trimble et al, 1993).…”

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confidence: 99%

Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease

Seymour

Mansi²,

Gallagher³

et al. 1994

Br J Cancer

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Summary This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Forty-seven patients participated, 20 of whom had received more than one prior treatment. Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of patient size), was given for 14 days on a 21-day cycle. However, after encountering toxicity, the schedule was modified to 7 days' treatment escalating to 10 then 14 days if well tolerated. Among 41 assessable patients there were two complete and eight partial objective responses (24% response rate; 95% confidence interval 12-41%). Nine further patients (22%) had stable disease, four with a sustained fall of > 50% in CA-125. Median duration of response or stable disease was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe myelotoxicity occurred, with two treatment-related deaths. Risk factors for severe toxicity were: performance status 3; hepatic impairment; renal impairment. We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy. It has significant toxicity which may be avoided by appropriate patient selection and an escalatingduration schedule.Platinum-based chemotherapy protocols have high initial response rates in patients with epithelial ovarian cancer. However, when the disease is primarily resistant, or when relapse occurs within a year, the prospects for second-line treatment are bleak. Phase II studies in this situation, either with single agents (Sutton et al., 1989;Coleman et al., 1989;1990;Manetta et al., 1990) or with combination chemotherapy (Belinson et al., 1986; Benedetti-Panici et al., 1990;Pater et al., 1987), have generally yielded few responses, of short duration. Even the promising new agent, taxol, gives responses in only 20-30% of this group of patients (Einzig et al., 1992;McGuire et al., 1989; Trimble et al., 1993).Platinum-resistant cell lines show little or no crossresistance to etoposide in vitro, making it a potential candidate for use either in combination with platinum as primary treatment or, later, as second-line treatment for this disease. In the five previously reported studies using singleagent etoposide as second-line treatment, a total of 247 patients were treated, with 51 responses (complete and partial responses; 21%). These studies all employed 3 or 4 day intravenous or oral schedules (Kuhnle et al., 1988; Kavanagh et al., 1989;Eckhardt et al., 1990;Hillcoat et al., 1985;Hansen et al., 1990).Etoposide interacts with topoisomerase II, which is active during the late S and early G2 phases of the cell cycle. It is consequently schedule dependent in vitro (Hill et al., 1981), and studies in small cell lung cancer (SCLC) hav...

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