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Adverse effects requiring discontinuation of cis-platinum therapy are usually noted after administration of 600 mg/m2 cis-platinum. Metabolic and therapeutic effects of high (greater than 1 g/m2) cumulative lifetime doses of cis-platinum were reviewed for 20 patients treated with multiple courses of chemotherapy for metastatic, recurrent ovarian carcinoma. Median survival in this selected group is 65 months. Common abnormalities included anemia, hypomagnesemia, and elevated renal functions. No patient required cessation of treatment because of metabolic changes and in no case did the abnormality compromise the patient's activities of daily living. We conclude that, in selected patients, repeated treatment, regardless of cumulative dose, with cis-platinum-based chemotherapy can be well tolerated and may be of therapeutic benefit.

Records of 15 patients with stage III and IV malignant mixed mesodermal tumors of the ovary treated between 1977 and 1988 were reviewed. All patients had primary surgery; 13 were given postoperative chemotherapy including doxorubicin and cis-platinum. Median survival for patients receiving chemotherapy is 16 months; 62% were alive at 12 months and 31% at 24 months. Progression-free responses were seen in 85% of treated patients and 55% of these recurred. All recurrences involved the pelvis and were predominantly mesenchymal. Serum CA-125 values accurately reflected tumor presence in 82% of tested patients. Cytoreductive surgery followed by treatment including doxorubicin- and cis-platinum-based chemotherapy is effective in treatment of disseminated ovarian mixed mesodermal tumors, but additional components must be added to achieve durable responses and consistently prolonged survivals.

Nineteen patients with advanced ovarian adenocarcinoma were treated with cis-dichlorodiammineplatinum(II) (DDP), 50 mg/m2 as an iv bolus once every 3 weeks. Prior treatment had exhausted other chemotherapeutic options or damaged the bone marrow sufficiently to contra-indicate treatment with standard drugs. All patients had evaluable tumors and evidence of failure of prior therapy. DDP produced objective responses, relieved symptoms due to tumor, and improved the patients' quality of survival. There were no serious hematologic complications due to therapy except anemia.

The combination of etoposide and cis-platinum was evaluated in the treatment of advanced ovarian cancer. Of 13 treated patients, 4 demonstrated complete clinical responses and 3 demonstrated partial clinical responses. The mean progression free interval was 14 months+ for the complete responders and 8.3+ months for the partial responders. The 100 mg/m2 dose of etoposide appears to be critical in attaining response. This etoposide and cisplatinum combination appears to be effective as a salvage regimen in ovarian carcinoma.

A 62-year-old woman with a diagnosis of metastatic fallopian tube carcinoma was treated with cis-platinum and doxorubicin (Adriamycin) at a dosage of 50 mg/m2 intravenously every 3 weeks. After the 10th course of cis-platinum and doxorubicin, she complained of headache and inability to see. Physical examination was compatible with cortical blindness. The brain scan and computed tomographic scan were normal. Visual evoked potentials showed a delay in latency. Visual acuity completely returned over the next months, but right homonymous hemianopia persists. The temporal relationship between the findings and the treatment with platinum implicates this drug as the possible causative agent in the cortical blindness.

Intraperitoneal administration of chemotherapy in ovarian carcinoma is currently under investigation. Numerous recent publications have described clinical studies employing a variety of chemotherapeutic drugs. Little information exists regarding the delivery systems employed or the complications encountered. This study reviews our experience with "single-use" and "long-term" catheters. Thirty-three catheters were placed in 28 patients. Of these catheters, 12 were long-term Tenckhoff catheters and 21 were temporary single-use catheters. Both types of catheters had complications associated with their usage. However, there was a dramatic difference in the number and severity of complications when the two groups were compared. Sixty-seven percent of the Tenckhoff catheters were associated with complications. Nineteen percent of the patients with single-use catheters experienced complications. This 19%, however, represented only 3.8% of the total number of single-use catheter insertions. In our hands, the temporary percutaneous approach has been a safe one, which is technically easy to perform with minimal complications.

Between 1974 and 1982, 273 patients with epithelial cancer of the ovary (International Federation of Gynaecology and Obstetrics Stages III and IV) were randomized in four therapeutic trials. In Trial I Adriamycin plus cisplatin versus cisplatin alone versus thiotepa plus methotrexate was tested. The superiority of Adriamycin plus cisplatin in producing the best response rate led to its use as the reference arm in subsequent trials. All investigational arms included cisplatin plus other drugs (cyclophosphamide, Adriamycin, hexamethylmelamine, and thiotepa) in various combinations. Eligibility for second look required complete clinical remission and completion of at least 10 cycles of chemotherapy. To date, 73 second-look operations have been performed on randomized patients. An additional 43 nonrandomized patients underwent second-look procedures and are analyzed separately. Between 40% and 46% of patients treated with cisplatin regimens had no disease at second look. Cell differentiation and volume of postoperative disease did not influence response.

For 129 ovarian cancer patients failing prior chemotherapy, overall clinical response rates were: 21% with cisplatin, 36% with cisplatin plus doxorubicin, 52% with cyclophosphamide added to the two drugs, and 44% with hexamethylmelamine added to the three drugs. Median survival was six or seven months in each trial. Twenty-five percent of the patients survived nine months with cisplatin and 14 to 16 months with each of the three combinations. Characteristics associated with best rate of response included: performance status 1 (completely ambulatory), age greater than or equal to 50, residual tumor less than or equal to 5 cm, and two or less prior cytotoxic drugs. In multivariate analyses, performance status dominated, although age and possibly treatment (cisplatin versus others) were significant. With performance status removed from the model, all of the remaining factors became significant. Factors associated with best survival included: performance status 1, tumor size less than or equal to 5 cm, and complete or partial response. In a multivariate analysis for survival, performance status entered the model. In a series of analyses with performance status removed, tumor size or response entered the model. These findings provide reasons to study both treatment with cisplatin before disease progression reduces the number of favorable characteristics and systematic second attempts at debulking surgery.

Patients with advanced ovarian carcinoma, Stage III or IV (International Federation of Gynaecology and Obstetrics), were randomized to primary chemotherapy with doxorubicin (Adriamycin) and cisplatin plus or minus hexamethylmelamine, and cyclophosphamide (CHAP). The four-drug CHAP regimen produced a 57% complete clinical response rate and a 26% partial response rate for clinically evaluable patients. The median survival of CHAP patients is 25 months. The two-drug Adriamycin-cisplatin (AP) regimen produced a 43% complete response rate and a 35% partial response rate. The median survival is 18 months. The four-drug regimen produced a significantly longer median survival (28 versus 18 months) for patients with poorly differentiated tumors than for patients with well-differentiated tumors on either treatment. Examination of treatment failure or death by treatment, histology, and size of largest residual tumor and comparison to similar patients treated with AP in this and two preceding controlled trials also suggest that CHAP is superior to AP for patients with poorly differentiated tumors.

In a prospective controlled randomized trial, patients with advanced ovarian carcinoma (FIGO Stage III or IV) were treated with cis-diamminedichloroplatinum (II), (DDP), alone, DDP and Adriamycin (ADM), or Triethylenethiophosphoramide (ThioTEPA) and methotrexate (MTX). DDP alone produces objective responses in 31% of evaluable patients, ThioTEPA and MTX in 36%. The combination of DDP and ADM produces the best response rate, 80% (.01 less than P less than 0.25). The risk of progression or death is substantially reduced for the two DDP regimens combined when compared with ThioTEPA-MTX (P = .03). Multivariate analysis further suggests the superiority of the two DDP regimens because poorly differentiated tumors and large, greater than 2 cm, residual tumors failed to produce their usual adverse effect on prognosis when patients were treated with the two DDP regimens. Patients with poorly differentiated tumors or tumors of unknown grade treated with platinum or DDP-ADM experienced better survival than similar patients treated with ThioTEPA (P = .01).

The prophylactic Papanicolaou Test contributes in diagnosing dysplasias and carcinoma in situ of the uterine cervix with a realistic 100% cure. Surgery and radiotherapy improved considerably quantity and quality of life in stages 1 and 2 lesions. However, stages 3 and 4 have shown little improvement in results. Systemic treatment with chemotherapy offers hope for control. Most of the drugs are ineffective against squamous cell carcinoma of the cervix. Experimental and clinical trials with CIS-platinum (2) diamminedichloride (DDP) show effectiveness against cervical carcinoma. In an effort to individualize the treatment, a chemosensitivity testing (CST) is applied analogous to the radiosensitivity testing (RST). Basically, a control biopsy and posttest dose of DDP biopsies are studied to evaluate the response using objective morphological criteria. This safe, relatively simple, clinically applicable approach offers an objective dimension in selecting the patients and in monitoring the treatment. An important observation that gives this study an original authenticity is the fact that radiation and chemotherapy affects the cells in an identical way. This similar morphological reaction most probably means an analogous biological expression of cellular injury and necrosis of the neoplastic cells.

Twenty-four patients who had stage III or IV ovarian adenocarcinoma and had failed prior chemotherapy were treated with cyclophosphamide, adriamycin, and cis-dichlorodiammineplatinum(II) every 3 weeks. Twelve patients had objective responses and an additional six had subjective improvement. The median duration of survival for responders is 9 months. There were no instances of nephrotoxicity. Fluid management consisted of 1000-2000 ml of iv fluid without Lasix- or mannitol-induced diuresis. Patients responded after having failed radiotherapy or multiple-drug chemotherapy, including some who were 70-75 years of age or were greater than 50% bedridden. Patients with one- or two-drug prior chemotherapy had a higher response rate (ten responses among 17 patients) than those previously treated with three or more drugs (two responses among seven patients).