Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC. METHODS: Thirteen women with EOC underwent cytoreductive surgery (CRS) and HIPEC, with CDDP and PTX. Blood, peritoneal perfusate and tissue samples were harvested to determine drug exposure by high-performance liquid chromatography and matrix-assisted laser desorption ionization imaging mass spectrometry (IMS). RESULTS: The mean maximum concentrations of CDDP and PTX in perfusate were, respectively, 24.8±10.4 µg ml(-1) and 69.8±14.3 µg ml(-1); in plasma were 1.87±0.4 µg ml(-1) and 0.055±0.009 µg ml(-1). The mean concentrations of CDDP and PTX in peritoneum at the end of HIPEC were 23.3±8.0 µg g(-1) and 30.1±18.3 µg(-1)g(-1), respectively. The penetration of PTX into the peritoneal wall, determined by IMS, was about 0.5 mm. Grade 3-4 surgical complications were recorded in four patients, five patients presented grade 3 and two patients presented grade 4 hematological complications. CONCLUSIONS: HIPEC with CDDP and PTX after CRS is feasible with acceptable morbidity and has a favorable pharmacokinetic profile: high drug concentrations are achieved in peritoneal tissue with low systemic exposure. Larger studies are needed to demonstrate its efficacy in patients with microscopic postsurgical residual tumours in the peritoneal cavity.

Primary carcinoma of the fallopian tube.

BACKGROUND: Because of the rarity of fallopian tube cancer, clinical approaches have changed during the last 18 years. METHODS: Twenty-nine patients with fallopian tube cancer were treated at the Gynecologic Oncology Department of Milan University from 1970 to 1988. The mean patient age was 59 years. Parity, symptomatology and histology were considered. Distribution by stage was as follows: I, 11 (37%); II, 10 (34%); III, 8 (27%) according to the Dodson classification. Twenty patients (69%) underwent surgery followed by pelvic irradiation. Adjuvant chemotherapy was performed in the treatment of 5 women with stage I disease, 6 with stage II, and all 8 with stage III. RESULTS: Five-year overall survival was 41.38%: 47.6% at stages I and II, 25% at stage III. Radiotherapy has not been replaced by cisplatin-based multiagent chemotherapy. Optimal surgical debulking combined with accurate lymph node sampling are not followed by systematic use of repeat laparotomy. CONCLUSIONS: The procedures described in this work improve the clinical assessment and patient survival, and make different series comparable.

Adjunctive radiotherapy after radical hysterectomy in high risk early stage cervical carcinoma. Assessment of morbidity and recurrences.

Morbidity and prognostic factors were reviewed in 145 patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between January 1976 and December 1986. Ninety five patients received adjuvant postoperative external radiotherapy (average 4800 cGY). One hundred twenty patients were F.I.G.O. stage IB, and 25 were clinical stage IIA. Indications for adjuvant radiotherapy included 3 categories of patients with high risk factors: 1) pelvic lymph node metastases, 2) parametrial invasion and/or surgical margins involvement, 3) large volume, deep stromal penetration or uterine extension. Four percent of the patients suffered major gastrointestinal complications, 8.9% had major genito-urinary complications, 19 patients had lymphocytes and 2 patients complained of thromboembolic episodes. Of the 19 patients with major gastrointestinal or genito-urinary morbidity, 7 (38.8%) were related to radiotherapy. Thirty-nine patients had node involvement, 38 of these patients received radiotherapy and 5-year survival rate was 43.5% versus 87.7% in other cases (p < 0.001). Of the 14 patients with parametrial invasion and/or surgical margins involvement, 10 received radiotherapy and overall 5-yrs survival was 85.8%. Of the 37 patients related to third category of risk, 18 received adjuvant radiotherapy with 83.3% 5-yrs survival versus 94.7% of other 19 cases (n.s.). Patients treated with surgery alone had a better 5-yrs survival (96%) than those who received combination therapy (66.3%) (p < 0.001). Adjuvant radiotherapy increases the morbidity of radical hysterectomy, while it has a relative value in preventing local and distant recurrences. In view of reduced survival in high risk patients with node involvement, consideration should be given to adjuvant systemic chemotherapy in high risk cases.

[Microsurgical discectomy (Oswestry expriences with 42 patients)]. / Mikrosebészeti módszerrel végzett discectomia. (Oswestry tapasztalatok 41 beteg kapscán).

Authors reviewed the results of healing of 41 patients, operated with herniated disc, in whom the herniated disc was removed with the help of microscope. The clinical results are analysed in details and compared with the literary data. The indication of microdiscectomy, its execution and the postoperative tasks are also discussed.

[Prognosis factors in epithelial tumors of the ovary]. / Fattori di prognosi nei tumori epiteliali dell'ovaio.

87 patients treated for epithelial ovarian carcinoma between 1975 and 1986 were evaluated intensively. In all cases the original operation was followed by surgical reassessment to evaluate the result of adjuvant therapy and to study the cases without apparent disease. The actuarial survival rate after 3 years, by Kaplan-Meier calculation, demonstrated 73.5% survival in patients with negative second-look versus 32% in presence of positive reassessment (P less than 0.01). Surgical reexploration and histologic study were negative in 34 cases (39%). Original stage, histotype, histological grading, peritoneal washing and age of patients were considered for prognostic evaluation of the tumor. The absence of residual tumor (RT) at first surgery resulted in complete response after adjuvant therapy in 70.8% of women, versus 25.8% with RT greater than 2 cm (P less than 0.01). Negative second-look appears the most important prognostic factor for the evaluation of epithelial ovarian cancer (P less than 0.001).