isotretinoin and Ovarian-Neoplasms

Vascular endothelial growth factor (VEGF), a mediator of tumor-associated immunodeficiency, plays a key role in angiogenesis and is a prognostic factor in advanced ovarian cancer (AOC). Previously, we showed that low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) improved the tumor-associated immunodeficiency and decreased VEGF in patients with AOC. Here, we report long term follow-up of a group of patients with platinum-sensitive AOC who were treated with IL-2 and RA.. Sixty-five patients with AOC who had a clinical benefit from second line chemotherapy and elevated serum levels of VEGF were entered into the study from 04/98 to 04/05. Therapy consisted of low-dose subcutaneous IL-2 and oral RA, administered on intermittent schedules for up to 5 years.. A statistically significant improvement in lymphocyte and NK counts and a decrease in VEGF levels were observed with respect to baseline values among the 65 evaluable patients. Five-year progression-free survival and overall survival rate were 29% and 38%, respectively.. These data show that patients treated with low-dose IL-2 and RA have a statistically significant improvement in their lymphocyte and NK counts, a decrease in VEGF, and seem to have an improved clinical outcome.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Docetaxel; Female; Follow-Up Studies; Humans; Immunotherapy; Interleukin-2; Isotretinoin; Killer Cells, Natural; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Paclitaxel; T-Lymphocytes, Regulatory; Taxoids; Vascular Endothelial Growth Factor A; Young Adult

The primary objective was to assess whether low-dose Interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) could decrease serum vascular endothelial growth factor (VEGF) and improve the immune function of patients with advanced ovarian cancer (AOC) responsive to chemotherapy. The secondary end-point was to compare the response of these patients with that of a group of control patients, treated with standard care. Forty-four patients with AOC, responding to chemotherapy and with elevated serum levels of VEGF, were entered into the study from 04/98 to 12/02. After chemotherapy, patients received self-administered subcutaneous IL-2, 1.8x10(6) IU and oral RA, 0.5 mg/kg for 5 days/week for 2 consecutive cycles of 3 weeks, with a 1-week rest, for 1 year and with intermittent schedules for up to 5 years. Eighty-two well-matched controls were selected from a large cohort of patients of similar disease status, treated with standard therapies. A statistically significant decrease of VEGF was observed amongst the 44 evaluable patients. Lymphocyte NK counts and CD4+/CD8+ ratio improved with respect to both baseline values and controls. The progression-free survival (PFS) and overall survival (OS) curves showed a statistically significant improvement in IL-2/RA-treated patients. These preliminary data show that, after chemotherapy for AOC, the administration of low-dose subcutaneous IL-2 and oral RA is feasible, has low toxicity, is cost-effective and improves both PFS and OS.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cohort Studies; Disease-Free Survival; Female; Humans; Immunotherapy; Interleukin-2; Isotretinoin; Killer Cells, Natural; Lymphocytes; Middle Aged; Ovarian Neoplasms; Time Factors; Treatment Outcome; Tretinoin; Vascular Endothelial Growth Factor A

Twenty-two asymptomatic women with rising CA 125 levels after chemotherapy for ovarian cancer were entered into a trial of isotretinoin combined with calcitriol. Tumours were evaluated according to precise criteria based on serial CA 125 levels and by comparing regression slopes of CA 125 before and during therapy. There was no evidence based on CA 125 of any responses or significant change in tumour growth rate.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; CA-125 Antigen; Calcitriol; Female; Humans; Isotretinoin; Ovarian Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Congresses as Topic; Female; Head and Neck Neoplasms; Humans; Insurance, Pharmaceutical Services; Interferon-alpha; Isotretinoin; Medical Oncology; Melanoma; Ovarian Neoplasms; Societies, Medical; United States