Advanced Recurrent Ovarian Cancer Research Articles

Topotecan. A review of its potential in advanced ovarian cancer.

The topoisomerase I inhibitor topotecan has shown antitumour activity against a variety of tumour types in vitro and in vivo. Topotecan in combination with drugs that induce DNA damage generally results in synergistic killing of tumour cells in vitro. As the activity of topotecan is related to exposure time, the drug is administered by intravenous infusion either continuously or once daily over a 30-minute period for several consecutive days. A 30-minute infusion of topotecan 1.5 mg/m2 on 5 consecutive days every 3 weeks produced response rates of up to approximately 20% in patients with advanced ovarian cancer who had failed to respond to platinum-based regimens or relapsed after initial response to such regimens. No significant differences in efficacy were apparent between topotecan and paclitaxel in a phase III study in patients with recurrent ovarian cancer, although a trend in favour of topotecan was evident for all major efficacy parameters. Non-cumulative myelosuppression, including neutropenia, thrombocytopenia and anaemia, is the dose-limiting toxicity associated with topotecan. Myelo-suppression was significantly more common with topotecan than with paclitaxel in a single comparative study. Non-haematological adverse events in topotecan recipients are generally mild and include alopecia, nausea, vomiting, and other gastrointestinal problems. Thus, topotecan has modest efficacy in the treatment of recurrent advanced ovarian cancer, with clinical activity similar to that of paclitaxel in a large randomised phase III study in this setting. Combinations of paclitaxel and a platinum compound are being used increasingly for first-line therapy, although relapse rates remain significant. Topotecan is therefore a suitable second-line option, providing antitumour response for some patients whose disease has relapsed after, or is refractory to, platinum-based therapy. Its wider potential when used either alone or in combination regimens should become clearer from ongoing studies.

Complete parietal and visceral peritonectomy of the pelvis for advanced primary and recurrent ovarian cancer.

Advanced primary and recurrent ovarian cancer within the pelvis presents a difficult oncologic problem in management. Based on a failure analysis of ovarian cancer, a new procedure was devised for the complete surgical removal of all visceral and parietal pelvic surfaces. Resections included the uterus, ovaries, rectosigmoid colon, and the complete pelvic peritoneum, including the cul-de-sac of Douglas. An immediate low rectal anastomosis with a circular stapler was utilized in all patients. Intraperitoneal chemotherapy was employed on postoperative days 1-5 to prevent further implantation of cancer cells. The technical experience with 12 women is reported. The circular stapler resulted in no anastomotic leakage and no anastomotic bleeding. There were no postoperative deaths. These results suggest that complete pelvic peritonectomy combined with early postoperative intraperitoneal chemotherapy carries an acceptable morbidity and mortality, and is a new treatment strategy that may be considered for advanced malignancy in the pelvic cavity. This surgical technique may be pursued in an attempt to optimize the management of ovarian cancer with peritoneal seeding.

Altretamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cancer chemotherapy.

Altretamine (hexamethylmelamine) is a cytotoxic antineoplastic agent which appears to require metabolic activation. Metabolic intermediates may act as alkylating agents; however, altretamine is not directly cross-resistant with classical alkylating agents. Objective response rates to orally administered altretamine as salvage therapy in patients with advanced ovarian cancer were 0 to 33%, with disease stabilisation in a further 8 to 78% of patients. Response rates appear to be higher in patients who have responded to previous alkylating agent or cisplatin-based therapy. There is some evidence that addition of altretamine to platinum-based combination regimens used for induction therapy of advanced ovarian cancer may improve long term survival, particularly in patients with limited residual disease. Although altretamine displays some activity in small cell lung cancer, it is unlikely to have any clinical role in the management of non-ovarian cancer. Altretamine appears to be relatively well tolerated, with gastrointestinal, neurological and haematological toxicities being the main dose-limiting adverse effects. However, assessment of accurate incidence rates for these effects is complicated by the use of altretamine with cisplatin. On the basis of the emerging body of clinical evidence, altretamine appears to have a limited role in the treatment of persistent or recurrent advanced ovarian cancer, primarily in patients who are potentially platinum sensitive yet intolerant of platinum analogues. Additionally, altretamine may be added to platinum-based regimens for induction therapy of advanced ovarian cancer. At the doses currently recommended, altretamine offers a reasonably well tolerated regimen that can be administered orally and is suitable for use on an outpatient basis.

Endocrine Factors in Common Epithelial Ovarian Cancer*

Ovarian cancer is responsible for 4% of all cancers in females and 6% of all their cancer deaths. Its mortality rate is greater than that of cervical and endometrial cancer together. The concentration of estrogen receptors (ER) rises and progesterone receptors (PR) falls in malignant ovarian tumors. In fact, ER and PR at present in 61% and 49% of malignant ovarian tumors respectively. 36% of these tumors contain both ER and PR. Further 69-90% of such tumors contain androgen receptors (AR). After (anti)hormonal agent therapy fails, physicians use progestins in combination with the synthetic antiestrogen tamoxifen in progressive or recurrent advanced ovarian cancer. The response rate for this treatment of ovarian cancer is only around 15%. Patients with malignant ovarian tumors with PR levels =or+ 50 fmol/mg tend to have a better prognosis than those with PR levels 50 fmol/mg. Neither age, stage of disease, nor tumor histology affect the prognostic value of PR. In vitro studies demonstrate that pure antiandrogens significantly inhibit about 60% of ovarian tumors. Another study also demonstrates that antiandrogen therapy alone may an effective endocrine therapy. As a result, the Gynecologic Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer if conducting a clinical trial on the effect of the antiandrogen flutamide on advanced or recurrent ovarian cancer. Researchers plan to investigate the effect of combining endocrine therapy with current standard chemotherapy. In fact, they intend to learn if combined chemo-endocrine therapy should be used as 1st line treatment for ovarian cancer.