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F Carnino

Publications and source records attributed to F Carnino.

At least 37 records · Page 2Linked to original sources
PubMed1990

Human GM-CSF in vivo: identification of the target cells and of their kinetics of response.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was given for three days (8 micrograms/kg/day) to 14 subjects who had solid tumors and normal hemopoiesis. The treatment induced a rapid 3- to 5-fold increase in the number of circulating neutrophils, eosinophils and monocytes. Lymphocytes, platelets and reticulocytes were unmodified during treatment. Activation of circulating neutrophils during GM-CSF treatment was demonstrated by a significant, increased release of neutrophil-derived platelet-activating factor after stimulation with N-formyl-methionyl-leucyl-phenylalanine, tumor necrosis factor-alpha or phagocytosis. The granulomonocytosis was dependent on increased bone marrow production of mature cells. Using the thymidine suicide technique, we observed that GM-CSF more than doubled the percentage of granulocyte-macrophage and megakaryocyte colony-forming units (CFU-gm and CFU-meg) and erythroid burst-forming units (BFU-e) in the S phase of the cell cycle. However, at the level of morphologically recognizable cells with autoradiography, we observed that GM-CSF increased the labeling index of the granulo-monopoietic cells, whereas that of the erythroblasts was unchanged. These data suggest that in accordance with in vitro observations, GM-CSF exerts its activity through all granulo-monopoietic lineages, whereas other cytokines (erythropoietin, thrombopoiesis-stimulating factors) may be needed to fully exploit the proliferative stimulus of GM-CSF on BFU-e and CFU-meg. After treatment discontinuation, the proliferative activity drops to values lower than before treatment, suggesting a period of relative refractoriness of marrow progenitors to the cytocidal effect of cell cycle-specific antineoplastic agents. This hypothesis is under evaluation in a controlled clinical trial where GM-CSF is given prior to chemotherapy.

Bone Marrow Transplantation↗
PubMed1990

Intraperitoneal cytosine arabinoside administered in sequence with systemic cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

After standard management of stage III-IV ovarian cancer patients by surgical reduction of tumor mass and subsequent cisplatin-based combination chemotherapy, eradication of residual intraabdominal disease remains a major clinical problem. In an effort to increase response to therapy without adding marrow toxicity, after laparotomy, 21 stage III-IV ovarian cancer patients were treated with systemic chemotherapy comprising cisplatin, doxorubicin, and cyclophosphamide (PAC) on Day 1 followed by intraperitoneal (ip) cytosine arabinoside (Ara-C) on either Day 8 or 14, every 28 days. Ara-C, an S-phase-specific drug, was administered ip to exploit the pharmacologic advantage of an ip regimen at a time when a possible PAC-induced recruitment of cells into the proliferative pool could further maximize cell kill. Kinetic features of ovarian neoplastic cells recovered from peritoneal washings were monitored during treatment by measurement of the thymidine labeling index (TLI): data from four patients indicate that there is an increase in proliferating cells on Days 8 and 14 after PAC treatment. Toxicity of treatment was acceptable. Although 95% of evaluable patients had more than 2 cm of residual disease, response was observed in 47% of patients. The therapeutic potential of this regimen should be tested in patients with small-volume disease after debulking surgery.

Aged↗
PubMed1989

The role of induction chemotherapy in inoperable ovarian cancer.

Thirty patients with bulky advanced ovarian cancer surgically not resectable, received combination chemotherapy (median of 4.1 cycles; range, 3-7) including cisplatin or carboplatin, followed by a second surgical effort. Clinical CR + PR was observed in 24/30 (80%) patients after chemotherapy. Our study deals only with these 24 patients, and the 6 patients who did not respond to chemotherapy are not part of this report. At debulking, 7/24 (29.1%) patients had a complete macroscopic resection; 9/24 (37.5%) patients had a partial resection (residual tumor less than 2 cm). These data suggest that debulking is feasible and successful after chemotherapy containing cisplatin or its derivative. Overall median survival from diagnosis was 18.9 months; the 3-year survival rate was 28%. Median progression-free survival from diagnosis was 13.5 months. The results observed in our study indicate that the use of induction chemotherapy can play an important role in increasing the chances of optimal debulking in patients presenting with unresectable ovarian cancer.

Adult↗
PubMed1989

Kinetics of human hemopoietic cells after in vivo administration of granulocyte-macrophage colony-stimulating factor.

The kinetic changes induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) on hemopoietic cells were assessed in physiological conditions by administering GM-CSF (8 micrograms/kg per d) for 3 d to nine patients with solid tumors and normal bone marrow (BM), before chemotherapy. GM-CSF increased the number of circulating granulocytes and monocytes; platelets, erythrocytes, lymphocyte number, and subsets were unmodified. GM-CSF increased the percentage of BM S phase BFU-E (from 32 +/- 7 to 79 +/- 16%), day 14 colony-forming unit granulocyte-macrophage (CFU-GM) (from 43 +/- 20 to 82 +/- 11%) and day 7 CFU-GM (from 41 +/- 14 to 56 +/- 20%). The percentage of BM myeloblasts, promyelocytes, and myelocytes in S phase increased from 26 +/- 14 to 41 +/- 6%, and that of erythroblasts increased from 25 +/- 12 to 30 +/- 12%. This suggests that GM-CSF activates both erythroid and granulomonopoietic progenitors but that, among the morphologically recognizable BM precursors, only the granulomonopoietic lineage is a direct target of the molecule. GM-CSF increased the birth rate of cycling cells from 1.3 to 3.4 cells %/h and decreased the duration of the S phase from 14.3 to 9.1 h and the cell cycle time from 86 to 26 h. After treatment discontinuation, the number of circulating granulocytes and monocytes rapidly fell. The proportion of S phase BM cells dropped to values lower than pretreatment levels, suggesting a period of relative refractoriness to cell cycle-active antineoplastic agents.

Bone Marrow↗
PubMed1989

Phase II trial of mitozolomide in patients with advanced ovarian cancer. A study of the EORTC Gynecological Cancer Cooperative Group.

Twenty-seven fully evaluable patients with advanced ovarian cancer and documented disease progression despite cytotoxic treatment were treated with mitozolomide (NCS-353451) 90 mg/m2 as a 1-h infusion once every 6 weeks. None of the patients responded, one had stabilization of disease for 4 months. Haematologic toxicity was the major side effect with a nadir or white blood cell counts around day 40. Two patients died with severe leukopenia and septic shock. We conclude that mitozolomide is not active in this poor-risk group of patients.

Adult↗
PubMed1988

Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

Aged↗
PubMed1988

Moving-strip abdomino-pelvic radiotherapy after cis-platinum-based chemotherapy and second-look operation. A feasibility study in advanced ovarian cancer.

Sixteen FIGO stage IIB-IV ovarian carcinoma patients who completed six to 12 courses of a cisplatinum-based combination chemotherapy and with minimal (less than 2 cm), microscopic, or no residual disease at second-look laparatomy received moving-strip abdomino-pelvic radiotherapy. Radiation treatment was feasible with acceptable toxicity; two patients had to interrupt therapy--one pretreated with 12 PAC courses because of WHO grade III leukopenia and the other because of grade III diarrhea. A third patient required surgery because of intestinal obstruction 1 month after cessation of radiotherapy. In patients with minimal residual disease at second look, the therapeutic value of sequential radiotherapy was unsatisfactory (five of six progressed), while further investigations were warranted in patients with no or microscopic residuum after second-look operation.

Aged↗
PubMed1987

Chemotherapy with estrogenic recruitment and surgery in locally advanced breast cancer: clinical and cytokinetic results.

Thirty-nine patients with locally advanced breast cancer (T3b-4, N1-3 or inflammatory carcinoma) received 3 cycles of induction chemotherapy with estrogenic recruitment before surgery. The therapeutic regimen consisted of diethylstilbestrol (DES) orally on days 1-3, 5-Fluorouracil + Doxorubicin + Cyclophosphamide on day 4 q 21 days (DES-FAC). After surgery 6 additional cycles of chemotherapy (3 DES-FAC alternating with 3 DES-CMF with Methotrexate + F and C as in FAC) were administered. The objective response rate was 71.8% with 15.4% CR, and 56.4% PR; after surgery 36/39 (92.3%) patients were rendered disease-free. So far, 13 of 26 patients in stage IIIb have relapsed (9 of 13 with inflammatory carcinomas). Three-year survival and progression-free survival are 60% and 53.5%, respectively. Twenty-three of the 39 patients were subjected to serial tumor biopsies during the first DES-FAC regimen to allow for tumor-cell kinetic studies during DES and chemotherapy. A significant estrogenic recruitment occurred in 16 patients (69.6%), irrespective of estrogen-receptor status. At surgery, 3-4 weeks after induction chemotherapy, tumor proliferative activity was significantly depressed in comparison to basal values. These results indicate that breast cancer cells can be recruited in vivo with DES and that chemotherapy following estrogenic stimulation is effective and feasible with acceptable toxicity.

Adult↗
PubMed1987

Phase II trial of anaxirone (1,2,4-triglycidylurazol, TGU) in patients with advanced ovarian carcinoma: an EORTC Gynecological Cancer Cooperative Group Study.

Sixteen patients with advanced ovarian carcinoma were treated with anaxirone (1,2,4-triglycidylurazol, TGU), 600 mg/m2 every 4 weeks. Anaxirone was the second or later line of therapy. All patients had evaluable tumors and evidence of failure of prior therapy. None of the patients responded. Two had stabilization of the disease for 4 months. In one patient WHO grade 4 leukopenia and grade 4 thrombocytopenia were observed after the second TGU cycle starting on day 41 and persisted until the patient died due to tumor progression (day 50). No patient experienced thrombophlebitis.

Adult↗
PubMed1987

Cisplatin and cyclophosphamide in early epithelial ovarian carcinoma.

Toxicity and efficacy of adjuvant cisplatin-based chemotherapy were assessed in 41 patients with FIGO stage I-II ovarian carcinoma. Chemotherapy consisted of cisplatin 50 mg/m2 and cyclophosphamide 600 mg/m2 administered on a one-day schedule q 28 d for six courses. Inclusion criteria were based on appropriate staging procedures and absence of macroscopic disease after primary surgery; patients with stage IAi G1-G2 or with borderline tumors were excluded from the study. Second look laparotomy was performed 2 months after termination of chemotherapy. At 60 months the actuarial survival is 77.5%. Recurrences were observed in 8 patients; in 1 case relapse was diagnosed at second look laparotomy. Toxicity was acceptable with only 1 treatment drop-out due to reversible neurotoxicity. Our results demonstrate that short-term chemotherapy including cisplatin is a safe and effective regimen and is suitable for administration on a outpatient basis. In our experience second-look laparotomy has limited value for early detection of relapses.

Adult↗
PubMed1985

High dose cisplatin after failure of polychemotherapy containing cisplatin in ovarian cancer. Preliminary results.

A substantial percentage of patients with advanced ovarian cancer will progress or relapse after platinum-based front therapies and will require salvage chemotherapy. In order to evaluate feasibility and effectiveness of high dose platinum (HD-CDDP) nine patients with ovarian cancer were treated with HD-CDDP while progressing after conventional doses of the same drug. Cisplatin 40 mg/M2 d. 1----5 q. 28 days, was administered with forced chloruresis for a total of fifteen cycles. Preliminary results show a promising 44.4% response rate with acceptable toxicity: only one patient had to discontinue treatment because of severe combined toxicity including infection, mucositis, shaking tremors, ototoxicity and palmar hyperkeratosis.

Adult↗