title: Continuous low-dose GM-CSF as salvage therapy in refractory recurrent breast or female genital tract carcinoma.
abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]) is a powerful cytokine that is able to stimulate the generation of dendritic cells. Adjuvant treatment with continuous low-dose GM-CSF has been shown to prolong survival of stage III/IV melanoma patients. Data on continuous low-dose GM-CSF therapy in tumors other than prostate cancer are still lacking. This pilot trial was initiated in order to evaluate the efficacy and tolerability of continuous low-dose GM-CSF as salvage in various chemotherapy-refractory carcinomas. A total of 19 patients who had failed a median of 4 prior chemotherapies were included. Their malignancies included metastatic breast cancer, recurrent ovarian carcinoma, metastatic endometrial carcinoma, and recurrent squamous cell cancer of the cervix uteri. Continuous low-dose GM-CSF was delivered subcutaneously at a daily starting dose of 125 microg. GM-CSF was increased at 25-microg increments until a maximum of 250 microg was reached or when mild leukocytosis (10-20 g/L) was achieved, providing that the relative eosinophil count did not exceed 15%. Therapy was continued until progression or refusal by the patient. Toxicity was generally mild. Only one patient was withdrawn due to grade 3 fatigue. In three additional patients, temporary dose reduction was necessary because of grade 1 injection site reactions, which recovered spontaneously. Mild to moderate leukocytosis was obvious in 10 patients. Systemic hypersensitivity-like reactions did not occur and no patient required hospitalization for other life-threatening side effects. The objective response rate was 37%: 1 complete and 6 partial responses, 4 disease stabilizations, 8 progression of disease. Median response duration was 6 months. Notably, 6 of 7 responders but only 1 of 8 patients with disease progression developed leukocytosis during therapy. Therefore, we conclude that continuous low-dose GM-CSF has substantial activity in heavily pretreated patients with either metastatic breast cancer or female genital tract cancer. Achievement of mild leukocytosis seems to be a predictor of response.
authors.affiliation: Institute of Gynecologic Oncology, Bonn Comprehensive Cancer Network, Germany. praxis.kurbacher@online.ms
authors.forename: Christian M
authors.initials: CM
authors.lastname: Kurbacher
authors.forename: Jutta A
authors.initials: JA
authors.lastname: Kurbacher
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Cramer
authors.forename: Kerstin
authors.initials: K
authors.lastname: Rhiem
authors.forename: Peter K
authors.initials: PK
authors.lastname: Mallman
authors.forename: Ralf
authors.initials: R
authors.lastname: Reichelt
authors.forename: Uwe
authors.initials: U
authors.lastname: Reinhold
authors.forename: Ursula
authors.initials: U
authors.lastname: Stier
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cree
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D010865:Pilot Projects; D011994:Recombinant Proteins; D016879:Salvage Therapy; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D011994:Recombinant Proteins; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor