Efficacy of the association of 13-cis-retinoic acid (13cRA) and alpha-interferon 2a (alpha-IFN 2a) in moderate-severe cervical intraepithelial neoplasia (CIN II-III): a pilot study.

Recent in vitro studies have suggested a possible therapeutic synergism between alpha-IFN 2a and 13cRA in certain neoplasias, while encouraging in vivo findings strongly support the enhanced effectiveness of the two agents when used in combination. The specific aim of our study was to evaluate the efficacy and the toxicity of the association of 13cRA and alpha-IFN 2a in patients with CIN II and CIN III who refused surgical treatment. Twenty-one patients (aged between 25 and 58 years), of which 14 were CIN II and 7 CIN III, entered the study. 13cRA (orally at 0.5-1 mg/Kg/day) and alpha-IFN 2a (intramuscular at 3x10(6) I.U./day for the first 15 days, then 3 times/week for the following four weeks) were administered simultaneously for eight consecutive weeks. 13/21 (62%) histologically verified objective responses (6 complete and 7 partial) were achieved. We also obtained 8 stable diseases. Compliance was generally good and no delays in therapy due to toxicity were recorded (except for two patients presenting WHO degree III cutaneous and mucosal toxicity which regressed one week after suspending treatment). Human Papilloma Virus (HPV) was initially detected in 16/21 (76%) patients, while HPV negativization after treatment was observed in 3/16 (19%). Although preliminary and requiring long-term assessment, the encouraging results of this study confirm the need for further investigation on the role of systemic medical therapy in the treatment of CINs.

High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

PURPOSE: The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer. PATIENTS AND METHODS: One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2% had greater than 5 cm of residual disease; 29.6% had stage IV disease. RESULTS: Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8% v 32.8%, P = .05), thrombocytopenia (21.7% v 3.2%, P = .003), anemia (37.6% v 12.5%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4% v 6.3%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5% v low-dose 61.1%), pathologic complete response (CR) (9.6% v 18.1%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months). CONCLUSION: This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.

High-risk early-stage ovarian cancer. Randomized clinical trial comparing cisplatin plus cyclophosphamide versus whole abdominal radiotherapy.

From 1985 to 1989 70 patients with high-risk FIGO Stage I-II ovarian carcinoma entered a randomized trial comparing chemotherapy (CT: cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 day 1 every 28 days for 6 courses) versus whole abdominal radiotherapy (WAR) given according to the open-field technique (43.2 Gy/24 fractions to the pelvis and 30.2 Gy to the upper abdomen). Protocol violations occurred in 8 patients randomized to WAR who received CT because of their own and/or physician's decision. Since protocol compliance was poor and accrual low the study was prematurely closed. Treatment-related toxicity for patients receiving CT was mild and tolerable, consisting chiefly of controllable grade 3 emesis (71%). Grade 3-4 diarrhea was experienced by 28% of patients treated with WAR; severe enteritis requiring hospitalization was observed in 2 patients. Late bowel obstruction requiring surgery was observed in 1 patient. At a median follow-up of 60 months, 21 patients died and 23 relapsed. Five-year survival was 71% and 53% (p = .16), while relapse-free survival was 74% and 50% (p = .07) for CT and WAR, respectively. Although no firm conclusion can be drawn from the present study, a short-term CT, including cisplatin, appears a safe treatment in comparison to WAR.

Copper IUD emission and its effects on human cervical mucus: spermatozoa interaction.

PIP: Total copper concentrations in the cervical mucus of 90 IUD-free women were measured at different times in their menstrual cycle using an atomic spectrophotometer and a 'Perkin Elmer 303' graphite furnace. The same procedure was done in another 109 subjects using various types of IUD (9 Dalkon Shields; 4 Progestaserts; 8 Copper Ts; 10 Copper Ts; 5 ml Cu 250s; 73 No-Gravid 1s, and; 4 No-Gravid 2s). Another groups of 123 IUD users was studied (16 Copper Ts; 16 Gravigards; 60 No. Gravid 1s; and 31 No-Gravid 2s), as were 17 IUD-free women and 30 No-Gravid IUD users. The cervical mucus samples were subjected to some spermetozoa tests (drop-to-drop admixture and penetration test and Kremer Test). The copper values in all subjects were lower in the follicular than in the luteal phase of the menstrual cycle. Women with copper IUDs also exhibited higher copper levels than those with non-copper IUDs. Copper levels were highest (up to 3 times) with the No-Gravid devices, even when measured after 30 months from insertions. Daily copper losses were also found to be greatest with the No-Gravid devices, with the greatest losses occurring within the 1st 6 months. Estimated time for 50% loss was 4 years. In comparing interaction of spermatozoa with the cervical mucus of women with No-Gravid devices and those without IUD, lower migration distances and penetration densities were observed in the No-Gravid cases.^ieng

Histological and ultrastructural changes of the endometrium in women using inert and copper-coiled IUDs.

The authors examined biopsy material obtained from women wearing inert and copper-coiled IUDs, under the light and electron microscopes. Examination of this material leads to the conclusion that there are no specific lesion attributable to either type of IUD. It can also be said that lesions characteristic for an inflammatory reaction prevail over all other possible endometrial changes.