Dose escalation of carboplatin and cyclophosphamide supported by GM-CSF inthe treatment of patients with advanced ovarian cancer (FIGO III and IV) -a phase I study

Citation
D. Sieger et al., Dose escalation of carboplatin and cyclophosphamide supported by GM-CSF inthe treatment of patients with advanced ovarian cancer (FIGO III and IV) -a phase I study, ONKOLOGIE, 22(6), 1999, pp. 502-506
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
ONKOLOGIE
ISSN journal
0378-584X → ACNP
Volume
22
Issue
6
Year of publication
1999
Pages
502 - 506
Database
ISI
SICI code
0378-584X(199912)22:6<502:DEOCAC>2.0.ZU;2-0
Abstract
Background: Up to 75% of ovarian cancers are diagnosed in advanced, incurab le stage. Only one fifth of these patients survives 5 years despite radical surgery and adjuvant chemotherapy. The study evaluates dose escalation of carboplatin (CBDCA) and cyclophosphamide (CTX) in combination with myelosup portive therapy with granulocyte-macrophage-stimulating factor (GM-CSF) in the treatment of advanced ovarian cancer. Patients and Methods: 25 patients with ovarian cancer (FIGO stages III and IV) were registered and treated w ith escalating doses of adjuvant chemotherapy. Starting dose of CBDCA was 3 50 mg/m(2) and of CTX was 800 mg/m(2) body surface area, supported by granu locyte-macrophage-stimulating factor (GM-CSF) 5 mu g/kg body weight subcuta neously, days 4-14 of chemotherapy. Intra-patient dose escalation of chemot herapy was modified according to the degree of myelosuppression. Tumor rest aging was performed after Four chemotherapy cycles clinically and with radi ological evaluation and/or laboratory testings. Results: 104 chemotherapy c ycles in 23 evaluable patients could be analyzed. 91 chemotherapy cycles we re administered with GM-CSF. The planned therapy interval of 21 days could be met in only 28% of the cycles. In 61% of treatments a delay of therapy w as caused by persistent myelosuppression. 50% of the patients had grade-III leukopenia; and grade-IV leukopenia was seen in 20% of the patients. One t hird of the patients developed grade-IV thrombopenia. Hematologic nadirs we re observed between days 12 and 21 of the treatment cycles. Dose escalation of CBDCA was possible in 21% of the patients with a maximum tolerated dose of 460 mg/m(2) and of CTX in 39% with a maximum tolerated dose of 1,184 mg /m(2). Dose intensity (mg/m(2) body surface area/week) ranged significantly below the expected dose intensity due to therapy delays (p=0.0004 and p=0. 002 for CBDCA and CTX, respectively). The overall response rate was 65%, wi th a complete remission rate of 48%. In 6 out of 23 patients tumor progress ion (as best response) was observed. Median time to progression was 373 day s. 12 of 23 patients died in the follow-up period of 3.6 years. Conclusions A positive effect of GM-CSF was observed regarding low- to intermediate-ty pe leukopenias. Severe myelosuppression allowed only a minor dose escalatio n and caused marked therapy delays. Therefore, no escalation of dose intens ity was possible and the applied dose intensity ranged clearly below the in tended range.