Advances in the chemotherapy of gynecologic malignancies

Chemotherapy is playing an ever increasing role in the treatment of patients with the common gynecologic malignancies, including ovarian, cervical cancer, and endometrial cancer. Chemotherapy has its most defined role in the treatment of patients with ovarian cancer where virtually all patients will receive cytotoxic chemotherapy. There are four major areas of research in chemotherapy in gynecologic malignancies. In retrospective studies it has been demonstrated that dose intensity is an important factor in maximizing response rates. Clinical studies are now prospectively evaluating the importance of dose intensity, particularly with the new platinum analogue carboplatin. In addition, it has been demonstrated in endometrial cancer and cervical cancer that patients with poor prognostic features such as high grade tumours and large volume disease have a low probability of cure by standard modalities such as surgery and radiation. In this group of patients combined modality approaches are being evaluated. In addition, regional therapy, either in the form of intra-arterial therapy for patients with cervical cancer or intraperitoneal therapy for patients with ovarian cancer, is being investigated. The primary factor limiting the effectiveness of chemotherapy in gynecologic malignancies is the development of drug resistance. It has recently been demonstrated that several drugs such as taxol, ifosfamide, and hexamethylmelamine have activity in patients who have had previous treatment with platinum-based compounds. In addition, the mechanism associated with the development of drug resistance in ovarian cancer have recently been identified. Clinical trials have been initiated with compounds such as buthionine sulfoximine in an attempt to specifically reverse resistance associated with alkylating agents and platinum compounds.