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Combination chemotherapy with irinotecan (CPT-11) and platinum compounds is effective for treating cervical cancer. Nedaplatin (254-S) is a new cisplatin analogue that achieves a high response rate (53%) in patients with primary cervical cancer. We performed a phase I -II study of combination chemotherapy with CPT-11 plus 254-S for advanced or recurrent cervical cancer. The inclusion criteria were stage IV disease or recurrence. CPT-11 and 254-S were administered intravenously on day 1, while rhG-CSF (50 mg) was given on days 3 -12. This regimen was repeated after 4 weeks. Dose escalation was carried out in tandem (CPT-11/254-S: 50/70, 50/80, and 60/80 mg m À2 ). A total of 27 patients (stage IV ¼ seven, recurrence ¼ 20) were enrolled. The phase I study enrolled eight patients. At dose levels 1 and 2, no dose-limiting toxicities were observed. At dose level 3, the first two patients developed DLTs. The maximum tolerated dose of CPT-11 and 254-S was 60 and 80 mg m À2 , respectively, and the recommended doses were 50 and 80 mg m À2 . Grade 3/4 haematologic toxicity occurred in 67% in phase II study, but there were no grade 3 nonhaematologic toxicities except fot nausea or lethargy. In all 27 patients, there were two complete responses (7%) and 14 Partial responses (52%), for an overall response rate of 59% (95% confidence interval: 39 -78%). Among the 12 responders with recurrent disease, the median time to progression and median survival were 161 days (range: 61 -711 days) and 415 days (range: 74 -801 days). This new regimen is promising for cervical cancer.

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Effects of granulocyte colony-stimulating factor (G-CSF) on proliferation and differentiation of normal human endometrial stromal cells were investigated in an in vitro decidualization culture of stromal cells. Unstimulated stromal cells secreted little prolactin and G-CSF, whereas 8-Br-cAMP-stimulated stromal cells secreted higher levels. There was no relationship, however, between the levels of prolactin and G-CSF secreted from the stimulated cells. Detectable levels of prolactin secretion were not found in two of six stromal cell cultures stimulated with 8-Br-cAMP; however, these two culture supernatants contained high concentrations of G-CSF. Co-stimulation of the stromal cells with 8-Br-cAMP and G-CSF enhanced prolactin secretion from the stimulated cells in a G-CSF concentration-dependent manner without any change in viable cell numbers. However, G-CSF did not affect prolactin secretion or viable cell numbers of 8-Br-cAMP-stimulated decidualized cells. These results indicate that G-CSF enhances cAMP-mediated decidualization of human endometrial stromal cells in an autocrine or paracrine fashion.

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