Phase II study of Mitonafide in advanced and relapsed colorectal cancer.

BACKGROUND: This study investigated the antitumoral activity in colorectal cancer and toxicity of a 5-day continuous infusion of a new cytostatic agent, Mitonafide, that had previously shown to be neurotoxic when administered as a short daily x 5 days infusion. PATIENTS AND METHODS: Seventeen chemotherapy-naive patients with advanced or relapsed colorectal cancer and measurable disease entered the study. All but one received a 120-hour (5-day) continuous infusion of Mitonafide at a starting dose of 200 mg/m2/day every 3 weeks. Toxicity evaluation was performed after each course and response assessment every 2 courses using the standard World Health Organization (WHO) criteria completed by the "Mini-mental state" test for cognitive status examination. RESULTS: Sixteen patients received a total of 41 courses of Mitonafide which resulted to be severely myelotoxic. In total, 13/16 patients had WHO grade 3-4 neutropenia, 7 of them with infection, and the treatment had to be stopped in 3 patients after only 1 course due to excessive toxicity. No central nervous system toxicity was observed. No objective responses were evidenced. CONCLUSIONS: At the dose and schedule of administration used, Mitonafide is not active in colorectal cancer and induces severe myelotoxicity thus not deserving further studies in this indication.

Improving treatment of chemotherapy-induced neutropenic fever by administration of colony-stimulating factors.

BACKGROUND: Several randomized trials have tested the use of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in relieving chemotherapy-induced bone marrow suppression. However, the use of CSFs in the treatment of neutropenic fever remains virtually unexplored. PURPOSE: This study evaluated the benefits of adding CSF therapy to the standard antibiotic treatments given to cancer patients for chemotherapy-induced neutropenic fever. The usefulness of CSFs was quantified in terms of reducing the following: (a) the duration of neutropenia, (b) the length of hospitalization, and (c) the overall cost of the treatment. METHODS: A randomized trial was conducted to test whether the administration of either G-CSF or GM-CSF improved the outcome of standard antibiotic therapy (ceftazidime plus amikacin) in nonleukemic cancer patients with fever (> 38 degrees C) and grade IV neutropenia (absolute neutrophil count [ANC] < 500/mm3) induced by standard-dose chemotherapy. Of 121 patients who entered the trial, 39 received G-CSF (5 micrograms/kg body weight per day), 39 received GM-CSF (5 micrograms/kg body weight per day), and 43 received a placebo beginning just after the first dose of antibiotics. Treatments were continued for at least 5 days (7 days with clinically or microbiologically documented infections) or until 2 days after fever subsided and ANCs rose above 1000/mm3. RESULTS: The median duration of grade IV neutropenia (ANC of < 500/mm3) was 2 days in both CSF arms and 3 days in the placebo arm (P < .001). The median duration of neutropenia with an ANC of less than 1000/mm3 was also significantly shorter in patients receiving G-CSF or GM-CSF (P < .001). The median duration of fever was similar in the three arms. The median hospital stay was 5 days (range, 5-14 days) in the G-CSF arm, 5 days (range, 5-10 days) in the GM-CSF arm, and 7 days (range, 5-34 days) in the placebo arm (P < .001). The median time on CSF was 4 days in both treatment arms. The mean cost of overall treatment was reduced by $1300-$1400 in the CSF arms compared with the placebo arm (P = .11 for G-CSF versus placebo; P = .06 for GM-CSF versus placebo; P = .7 for G-CSF versus GM-CSF). CONCLUSIONS: Adding G-CSF or GM-CSF therapy to antibiotic treatment shortens the duration of neutropenia and the duration of hospitalization in patients with neutropenic fever. A statistically nonsignificant trend toward lower cost was observed in the CSF arms as compared with the placebo arm. IMPLICATIONS: The benefits of CSFs to cancer patients with chemotherapy-induced neutropenic fever merit further evaluation in large randomized trials.

Leiomyosarcoma of the soft tissues in a patient with nevoid basal-cell carcinoma syndrome.

A 57-year-old man was admitted with complaints of progressive anorexia, weight loss and right flank pain. He had been treated for basal-cell carcinoma of the skin 19 years before. On physical examination, eight moles in the face, back and left thigh were found along with palmar pits. In addition, a painful induration in his right thigh was evident. Biopsy proved that six moles were basal-cell carcinomas and the thigh mass a high-grade leiomyosarcoma. Computed tomographs revealed multiple metastases in the lungs and the liver. The patient was treated with epirubicin, with partial response, and subsequently with ifosfamide. He died 17 months after diagnosis. Whereas the world literature records several cases of soft tissue tumors in patients with nevoid basal-cell carcinoma syndrome, this is the first report of a simultaneous occurrence of leiomyosarcoma and nevoid basal-cell carcinoma syndrome.

Ovarian and extragonadal malignant germ-cell tumors in females: a single-institution experience with 43 patients.

From 1978 to 1992, 276 patients (pts) with MGCT were treated in our institution. Forty-three of the pts were female (15.5%). Median age at diagnosis was 20 years (newborn-70). Histology was dysgerminoma (D) in 14 pts (including 2 anaplastic D), endodermal sinus tumor (EST) in 9 pts, immature teratoma in 10 pts and mixed tumors in 10 pts. Primary locations were as follows: ovary (O) 33 pts and extragonadal (EG) 10 pts (pineal in 4 cases, mediastinum in 3, sacrum in 2 and pharynx in 1). Stage: I in 20 (16 O, 4 EG), II in 7 (5 O, 2 EG), III in 12 (10 O, 2 EG) and IV in 4 (2 O, 2 EG). Serum AFP was elevated in 20/22 non-dysgerminoma pts, HCG in only 5 pts and LDH in 15/36 pts. TREATMENT RESULTS: Ovarian tumors: all but one pt (biopsy only) underwent surgery: unilateral oophorectomy was performed in 15 pts and bilateral oophorectomy (+/- hysterectomy, +/- others) in 17 pts. Fourteen pts were rendered disease-free, 8 pts had residual tumor (RT) < 2 cm and 11 RT > 2 cm. Chemotherapy (PVB or BEP) was given to 28 pts, radiotherapy to 2 pts and no additional treatment to 3. Finally, 30 pts achieved complete response (CR) and none have relapsed at a median follow-up of 43 months. EG tumors: None of the pts underwent radical surgery. Radiotherapy was applied to 4 pineal tumors and BEP or PVB were given to all 10 pts. To date 6 pts are disease-free, 1 is alive with mature teratoma, 2 are alive with disease and 1 died of toxic effects. The projected overall survival of the series as a whole is 89% at 10 years, and it is significantly higher for pts without EST (p < 0.02) and for pts with AFP < 1000 (P < 0.01) and age < 22 years at diagnosis (p < 0.01). The projected event-free survival at 10 years is 80.4% (87.7% for ovarian tumors vs. 54% for extragonadal, p = 0.05). No events were recorded after 28 months. CONCLUSIONS: The present results reflect the dramatic effectiveness of cisplatin-based chemotherapy for ovarian MGCT and confirm that unilateral oophorectomy can preserve fertility without compromising cure. Age > 22 years, histology (EST) and serum AFP > 1000 ng/ml are possible prognostic factors (univariate analysis) to be tested in an independent body of data on cisplatin-treated patients.