A combination of low-dose prolonged infusional gemcitabine and oral treosulfan in platinum- and taxane-refractory Mullerian carcinomas: A phase II study

Abstract

5064 The GeT regimen - gemcitabine (dFdC) + treosulfan (TREO) - has been found to be active in metatastic melanoma and refractory epithelial ovarian carcinoma (EOC). However, the q3w regimen with dFdC at 1250mg/m2 day 1+8 and TREO at 5000 mg/m2 day 1 was associated with myelosuppression negatively influencing dose intensity and, consecutively, progression-free survival (PFS). Since maintaining cellular accumulation appears to be crucial for long-lasting responses, this phase II trial in platinum- and taxane refractory Mullerian carcinomas (MC) was set up using a modified q2w GeT protocol with dFdC at 450 mg/m2 (3 h infusion) day 1 and oral TREO at 1000 mg/m2 day 1–4. A total of 25 patients (pts) were included (EOC: n=24; papillary-serous endometrial carcinoma: n=1). Patients had failed a median of 2 prior Ctx (1: n=9; 2: n=6; 3: n=5; 4: n=2; 5: n=2) including platinum and paclitaxel in all, anthracyclines in 9 and topotecan or dFdC in either 4 pts. A total of 145 cycles were given with a median of 6 (range: 2–10). All pts had measurable or evaluable disease according to the RECIST and Rustin criteria, repectively. All treatments were evaluable for both toxicity and response. Anemia which was never therapy-limiting was frequent but exceeded NCI-CTC grade 2 in only 8/145 cycles (6%). Leukopenia > grade 2 was not observed. In one patient, interval prolongation was necessary due to febrile urinary tract infection. In another patient, treatment was terminated due to non-lethal pulmonary embolism. Other toxicities did not exceed NCI-CTC grade 1 nor did any other patient require hospitalization due to therapy-related toxicities. A total of 9 CR and 4 PR were recorded accounting for an objective response rate of 52%; 6 pts achieved SD and 6 pts progressed on GeT. The median progression-free survival was 29 weeks. Until now, only 5 pts have died, so that the median overall survival is not yet reached. Facing the intensive pre-treatment of the pts studied, it can be concluded that the modified GeT protocol is well tolerated and exhibits a promising clinical activity in MC refractory to both platinum and taxanes that warrants further exploration in large-scaled clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration L.a.n.c.e. Inc.