Experience with intraperitoneal alpha-2a interferon.

Eighteen patients affected with epithelial ovarian cancer have been treated by intraperitoneal alpha 2a-Interferon. The usual single dosage was 54 x 10(6) U at weekly intervals for four times (eight times in responders): 10 histologically confirmed complete remissions and 3 partial remissions have been obtained; the toxicity was represented by fever in the majority of the cases, by abdominal discomfort in some cases, and by a mild transitory neurological complication in 1 case. Seventeen of 18 patients were pretreated, and 11 of 18 had only cytologic and/or microscopic disease. alpha 2a-Interferon has proven to be very effective and moderately toxic in microscopic peritoneal disease of ovarian epithelial cancer previously treated with extensive surgery and intravenous cytotoxic chemotherapy.

Localized ovarian cancer: surgery plus chemotherapy.

Fifty-four patients were referred to Medical Oncology after operation for "limited" ovarian cancer; 7 were excluded because immediate restaging showed evidence of macroscopic spread to structures outside the true pelvis, and 10 will be considered separately because of microscopic spread shown only by cytology. Thirty-seven patients (31 stage I and 6 stage II) were accordingly accepted as "localized", because peritoneal cytology and diaphragm and omental plus parietal peritoneum histology could rule out the spread to the large abdominal cavity. Some of the referred patients had been operated in nearby hospitals; the Padua GYN Cin. performed 14 of the 37 first surgery operations and 30 of the 37 second look operations. All patients soon after surgery underwent first-line chemotherapy with 5 courses of high dose adriamycin plus cyclophosphamide for 4 months, then surgical second look, and second-line non-cross-resistant chemotherapy for 3 months. During the second look the organ and tissue removal was completed in those 21 patients having received "limited" first surgery. Two patients died within 5 years from admission, so that the overall 5 year actuarial survival from referral is 93% for the entire group with 11 patients still at risk; 87% are disease free 5 years after the second look with 7 at risk. Subdivision of the patients according to "adequate" vs. "limited" first surgery, may select a group (the "adequate" one, composed of 16 patients) completely free from relapses, up to now. The complex therapeutic program described seems to offer long term relapse-free survival to the majority of patients, while the few failures seem closely related with inadequacies of the initial surgical procedure.

Lipid bound sialic acid in cancer patients.

Serum lipid-bound sialic acid (LSA) was measured with a recently described procedure in 108 healthy subjects and in 138 patients with a variety of solid tumors and hematologic malignancies. At the time of serum sampling, 128 patients had active disease and 10 patients had no evidence of disease. LSA was elevated in 104 of 128 (81.2%) patients with active disease, while carcinoembryonic antigen, analyzed in 74, was elevated only in 21 (28.4%) (P less than 0.05). Sensitivity of the serum LSA test ranged from 66% for breast and gastrointestinal cancer to 92% for lung cancer. In patients with lung cancer, ovarian cancer or Hodgkin's disease, LSA was correlated with the extent of disease and it also proved to be useful in following the course of disease. Our preliminary data indicate that this test can be used as a monitor of tumor burden.

Peptichemio in pretreated patients with ovarian cancer.

From January 1978 to October 1982, 47 patients with histological diagnosis of epithelial cancer of the ovary received peptichemio (PTC) at a dose of 70 mg/m2 (maximum, 120 mg total) every 15 days. Forty-two patients are now evaluable: 27 with stage III and 15 with stage IV disease. All patients but four with stage IV disease had been pretreated and had received at least one drug combination (median, three drugs per patient, including alkylating agents). Before the administration of PTC, the tumor extension in the abdomen was carefully assessed in all patients: ten patients had residual tumor less than 2 cm in diameter, while 32 patients had tumor greater than 2 cm in diameter. Objective responses were obtained in ten patients (23.8%): six complete remissions and one partial remission were observed in stage III patients and one complete remission and two partial remissions were observed in stage IV patients. Of the ten responding patients, eight had tumors less than 2 cm in diameter before receiving PTC. The median duration of response was 16 months. The most frequent side effects were myelosuppression and phlebosclerosis. Bone marrow depression was a common finding after the third course in heavily pretreated patients. Accordingly, in these patients a schedule interval of 3 weeks should be more appropriate. Since most of the responders were in the "small tumor" category, PTC appears to be an active drug in patients with ovarian cancer having small tumors (less than 2 cm). On the other hand, the response rate in a nonselected population of patients remains to be clearly defined with further studies.

Clinical significance of plasma lipid-bound sialic acid (LBSA) and carcinoembryonic antigen (CEA) in gynaecologic cancer patients.

A comparison between plasma lipid-bound sialic acid (LBSA) and carcinoembryonic antigen (CEA) in gynaecologic cancer patients has been performed. The LBSA level appears more specific then the CEA, especially for ovarian cancer. This finding has promoted a longitudinal study to show if LBSA test may prove a reliable marker of disease in ovarian cancer patients.

Role of second look laparotomy in multidisciplinary treatment and in the follow up of advanced ovarian cancer.

Surgical re-examination after first line surgery followed by chemotherapy is an absolutely necessary step in the course of integrated treatment of advanced ovarian epithelial tumours. Our personal experience of surgical re-staging and reductive surgery in 48 patients affected by ovarian tumours stage III and IV (FIGO), by laparotomic second look is reported. Repeated surgery succeeds in further reducing the neoplastic deposits or radicalizing the first intervention in 33% of the overall series; in 52% of the cases, the second look was negative for neoplasia; in 16% only, despite tumour finding no reductive surgery was possible. If only the cases presenting residual neoplasia after primary surgery are taken into account, tumour debulking was possible in 44% of the patients. The analysis of this series fully confirms the preliminary statement that the smaller the residual neoplasia after surgery, the greater the chances of success for chemotherapy in ovarian cancer. It confirms as well that the laparotomic second look is the only currently available way to usefully assess the full remission of the disease.

Role of computed abdominal tomography (C.A.T. Scan) in the follow up of ovarian tumors.

This study evaluates the possible use of computed tomography not as an alternative diagnostic method but, rather, as a supplement to laparotomy in patients treated for ovarian cancer. The following conclusions can be drawn: in patients presenting no clinical evidence of persistent or relapsing disease C.T. Scan is not a mandatory but, rather, an optional test since it entails 25% false negatives, a 66.6% predictive value and because the involved patients will need, in any case, a further intervention. Conversely, C.T. Scan is clearly indicated in patients presenting clinical evidence of disease. It can prove helpful in detecting metastases in areas that prove difficult to be clinically examined; in assessing whether the retroperitoneal areas conceal neoplastic tissue or in planning the right operation for masses that have been palpated only before chemotherapy, and then in regression. When, despite chemotherapy, tumour progresses, surgery may became useless, and the C.T. Scan may therefore prove helpful in defining the condition and guiding non surgical treatment. Therefore, in the follow up of ovarian cancer the C.T. Scan may be performed on the basis of clinical course, instead than on a rigid aprioristic planning.

A planned prospective study of combined treatment in stage III epithelial ovarian cancer.

In a planned prospective study 39 consecutive patients with stage III ovarian cancer have been admitted in two years. All patients have received initial extensive surgery followed on as out patients basis by 5 courses of A-Cy chemotherapy and by a second operation and further non cross resistant chemotherapy with Platinum, Hexamethyl-Melamine, Polymelphalan; 24 have been found pathologically free of disease at second surgery, and 34/39 are clinically free of disease while reporting. These data, exactly collected and evaluated are consistent with our (previously reported) empyrical observation that adjuvant surgery interspersed with courses of aggressive chemotherapy may render free of disease the majority of patients, prolong survival, and possibly cure a portion of this population.

Fibrinolysis in ovarian cancer.

Coagulation disorders, including thromboembolic phenomena and disseminated intravascular coagulation are recognised as a complication of neoplastic disease. In the present study the Fibrinogen Degradation Products (F.D.P.) were determined in 26 patients with Advanced Ovarian Cancer (stage III and IV FIGO) (mean = 38.1; S.D. = 37.6) and in ten healthy patients considered as controls (mean = 2.7; S.D. = 13). The significative difference (p less than 0.05) between the two groups points in evidence an increasing activation of Ffibrynolytic processes. The F.D.P. determination has revealed a good correlation (p less than 0.001) with the tumor extension as showed by the difference between third stage with large tumor masses (late) (mean = 44.5; S.D. = 24.5) and third stage with minimal residual disease after reductive surgery (early) (mean = 6.7; S.D. = 5.7).