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Biomedical subjects

P F Conte

Publications and source records attributed to P F Conte.

175 records · Page 10Linked to original sources
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A randomized trial of chemotherapy with or without estrogenic recruitment in locally advanced breast cancer. North-West Oncology Group (GONO) Study, Italy.

The present phase III trial was carried out to verify whether a kinetic recruitment induced by low doses of diethylstilbestrol (DES) could increase the killing efficacy of chemotherapy in patients with locally advanced breast cancer. One-hundred and seventeen untreated patients with locally advanced breast cancer (stage IIIA/IIIB) were randomized to receive 3 courses of primary chemotherapy consisting of cyclophosphamide (600 mg/m2 i.v.), doxorubicin (50 mg/m2 i.v.) and fluorouracil (600 mg/m2 i.v.) (CAF) on day 1, or DES-CAF (DES, 1 mg orally days 1-3, CAF on day 4). The courses were repeated every 3 weeks. The patients who achieved an objective response were submitted to mastectomy followed by 3 courses of CAF alternated with 3 courses of CMF (cyclophosphamide, 600 mg/m2 i.v.; methotrexate, 40 mg/m2 i.v.; fluorouracil, 600 mg/m2 i.v.), with or without DES. The two treatment arms were well balanced in terms of clinical and pathologic features. There was no significant difference in response rates to induction chemotherapy between the two treatment arms (objective response rate, 63.3% for CAF and 56.1% for DES-CAF). Median overall survival was 49 and 47 months and median progression-free survival was 24 and 21 months for CAF and DES-CAF patients, respectively. Toxicity was not significantly different in the two groups, with the exception of leukopenia: DES chemotherapy was significantly more myelotoxic than the standard treatment, which resulted in a significant reduction in the actual dose intensity. In spite of the attractive experimental evidence, we conclude that so far there is no clinical advantage in the combination of estrogen and chemotherapy. Further research is needed to investigate different schedules of chemotherapy and hormones, or to test the possibility of combining various mitogens.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Suramin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in metastatic colorectal cancer patients resistant to 5-FU+LV-based chemotherapy.

AIMS AND BACKGROUND: Suramin has been shown to be of interest as a potential new anticancer agent because of its capacity to inhibit the binding of several growth factors to their receptors and to inhibit the growth of cancer cells in vitro. Since multi-autocrine loops involving growth factors which are antagonized by suramin have been demonstrated in colorectal cancer, we previously evaluated the activity of suramin in patients with advanced colorectal cancer. Interestingly, in this study three patients who had received 5-FU+LV after suramin, although heavily pretreated with fluoropyrimidines, obtained an objective response. This observation was intriguing as it might have been that suramin had changed the biology of the tumor, making it sensitive to 5-FU+LV. We therefore conducted the present study to investigate the possibility that suramin might overcome the resistance to 5-FU+LV. METHODS AND STUDY DESIGN: Only colorectal cancer patients with metastatic and progressive disease during 5-FU+LV-based chemotherapy were eligible for this study. Suramin was administered for eight weeks at doses determined by means of a computer-assisted dosing algorithm that used Bayesian pharmacokinetics to maintain suramin plasma concentrations of 200-250 microg/ml. 5-FU was administered weekly at a dosis of 450 mg/m2 halfway through a two-hour infusion of I-LV 250 mg/m2 starting one week after the initiation of suramin for a maximum of 26 weeks. RESULTS: Treatment was relatively well tolerated, but no objective responses were observed after the accrual of 13 patients in the first stage of the trial. Consequently, the trial was interrupted according to the initial two-stage sampling design. CONCLUSIONS: The present study does not support the hypothesis that suramin might overcome resistance to 5-FU+LV and its use in colorectal cancer is not recommended.

Aged↗
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Intrahepatic chemotherapy with floxuridine, leucovorin and dexamethasone in continuous infusion and mitomycin-C bolus in unresectable hepatic metastases from colorectal cancer: a phase II study.

BACKGROUND: Intrahepatic continuous infusion FUDR induces a 50% response rate in patients with hepatic metastases from colorectal cancer. Lower rates have been observed in pretreated patients. The combination of floxuridine plus leucovorin has obtained over 70% responses, with high hepatic toxicity. The use of dexamethasone can decrease hepatic toxicity. A randomized study reported an increase in response rate and a decrease in hepatic toxicity in a group of patients treated with floxuridine plus dexamethasone compared to a group receiving only floxuridine. Moreover, the combination of mitomycin C, carmustine and floxuridine is also effective in pretreated patients. METHODS: On such premises, since July 1993 we have treated 39 patients affected by unresectable hepatic metastases from colon carcinoma (26 patients) and rectal carcinoma (13 patients) with the combination continuous infusion of floxuridine (0.20 mg/kg per day) + leucovorin (7.5 mg/m2/day) + dexamethasone (20 mg on days 1 to 14) and bolus mitomycin C (10 mg/m2 on day 1) via the hepatic artery. Cycles were administered every four weeks. There were as 28 males and 11 females, with a median age of 64 years (range, 39-75) and a median PS = 0. Twenty-two patients were pretreated with systemic chemotherapy including 5-fluorouracil plus leucovorin. Total number of cycles was 189, with a median of 6 cycles per patient (range, 1-12). RESULTS: Of 39 patients 37 were assessable for response (2 patients were not assessable because they stopped chemotherapy for occlusion of the catheter after the first cycle). There were 3 complete responses (1 in a naive patient and 2 in pretreated patients), 16 partial responses (11 in pretreated patients and 5 in chemonaive patients), 4 minor responses, 4 stable disease and 10 progressive disease. The overall response rate was 51.3% (95 Cl, 51.3-86.7%). Median time to progression was 6 months (range, 1-34+). Overall survival was 18 months (range, 1-34+). Of 39 patients, 36 were assessable for toxicity (WHO) (3 patients died after the first cycle for progression of disease): diarrhea and nausea-vomiting grade 3-4 occurred respectively in 15 (41%) and 3 patients (8%); hepatic toxicity was mild. CONCLUSIONS: The treatment we used showed an elevated activity in liver metastases from colorectal cancer even in patients pretreated and resistant to systemic chemotherapy, although toxicity grade 3-4 diarrhea occurred in approximately 40% of the patients.

Adult↗
PubMedDate not supplied

[Experimentation with Di Bella polychemotherapy in Tuscany].

The study reports the experience of Di Bella Treatment (an unconventional treatment for cancer) for advanced cancer patients in Tuscany. A total of (38 + 140 + 463) patients were treated (38 phase II study, 140 observational study and 463 distributional study) and all the case report forms were collected and analyzed in the Regional Coordinator Center of Pisa. No objective response was observed; as of May 31, 1999 63 patients are in stable disease (1 phase II, 3 observational and 59 distributional study). Percentage of interruptions to treatment due to death, refusal and toxicity were similar between patients O and D, while there are significant differences in terms of progressive disease (O = 52% vs D = 18%) and number of losts to follow up (40% in distributional study). The median duration of treatment was 2.31 months (range: 0-15) in the observational study and 3.2 months (range: 0-13) in the distributional study. The median overall survival time (4.5 months) and the median time to disease progression (2.7 months) were calculated by Kaplan-Meier Method and were based on all treated patients (intention to treat population). Follow-up of the study was stopped at 31.05.1999.

Aged↗
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p53 status is neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen.

BACKGROUND: The aim of this study was to assess the relationship between p53 status and the clinical outcome of patients with advanced ovarian cancer treated with a paclitaxel-based regimen. PATIENTS AND METHODS: The investigation was conducted on 38 patients with FIGO stage III-IV ovarian cancer from whom tumor tissue samples for p53 protein immunostaining were obtained during initial cytoreductive surgery. All these patients subsequently received six cycles of first-line combination chemotherapy with paclitaxel 175 mg/m2 (3-hour infusion) plus carboplatin AUC 6 with or without epidoxorubicin 75 mg/m2. RESULTS: Positive p53 immunostaining was detected in tissue samples collected from 24 (63.2%) ovarian cancers. A clinical complete response was obtained in 14 (58.3%) of the 24 patients with positive p53 immunostaining compared to 9 (64.3%) of the 14 patients with negative p53 immunostaining (p = 0.717). A pathological complete response was found in 6 (25.0%) of the former compared to 4 (28.6%) of the latter (p = 0.956). Similarly, survival did not correlate with p53 status (p = 0.1271). DISCUSSION: p53 status seems to be neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. These results are consistent with experimental data showing that paclitaxel cytotoxicity in ovarian cancer is likely to be mediated by a p53-independent pathway.

Adult↗
PubMedDate not supplied

Intraperitoneal chemotherapy with carboplatin and interferon alpha in the treatment of relapsed ovarian cancer: a pilot study.

In ovarian cancer patients intraperitoneal chemotherapy confers pharmacokinetic advantages and appears an attractive way to improve the efficacy of certain antineoplastic agents. Intraperitoneal carboplatin and interferon alpha have been separately evaluated in ovarian cancer "with promising results". We report a phase I-II pilot trial of intraperitoneal carboplatin 400 mg/sqm plus interferon alpha 25 x 10(6) U q 28 d in 16 patients (pts) previously treated with intravenous cisplatin based chemotherapy. All the patients had relapsed (11 pts) or refractory (5 pts) disease; residual tumors were less than 2 cm in 10 pts and greater than 2 cm in 6 pts. Local and general toxicities were moderate, with neither WHO grade 4, nor neurotoxicity and ototoxicity. Myelotoxicity was the most frequent side effect. Among 14 evaluable pts, objective responses were observed in 6 pts (42.8%) including 3 pts with pathologically confirmed complete response (21.4%); six more pts presented prolonged disease-free survival. Response occurred in both categories of pts with greater than or less than 2 cm residual disease, also in pts refractory to prior intravenous cisplatin. The proper role of intraperitoneal treatment cannot be exactly defined without large randomized trials designed to compare intraperitoneal to intravenous drug administrations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Human myeloma].

Explore the source record for details and available documents.

B-Lymphocytes↗
PubMedDate not supplied

Biology of the human myeloma cell population. II. Cytokinetic characteristics.

A kinetic study of five human myeloma cell populations before and after chemotherapy using cytochemical and autoradiographical techniques showed: 1. a large number of cells, with a DNA content intermediate between 2c and 4c, that did not incorporate thymidine ('U' cells) and were indicative of ineffective myelomapoiesis; 2. non cell cycle-specific (cyclophosphamide) followed by cell cycle-specific (vincristine) treatment led to an increase in the 3H-thymidine labelling index (LI) and activation of macromolecular synthesis (increased uridine and leucine uptake and actinomycin binding capacity) pointing to early cell recruitment. A high percentage of 'U' cells can be found even after therapy. The LI variations make it clear that recruitment after therapy is overestimated by at least 40% due to ineffective myelomapoiesis. In the light of this and previous personal studies, we propose a kinetic pattern: the myeloma population may be seen as a highly differentiating population whose non-proliferating cells cannot re-enter the cycle. By contrast, the acute leukemia populations are unable to differentiate, and the non-proliferating cells (G0) can be recalled into the cell cycle.

Cell Cycle↗
PubMedDate not supplied

In vivo cytokinetic effects of recombinant human growth hormone (rhGH) in patients with advanced breast carcinoma.

We have investigated the possibility of inducing a kinetic recruitment of breast cancer cells by the in vivo administration of recombinant human Growth Hormone (rhGH). Twelve patients with advanced breast cancer received rhGH i.m. for 2 days immediately before the first course of chemotherapy. The following biological parameters have been evaluated before and 24 hours after rhGH administration: tumor TLI, tumor IGF-I content, serum IGF-I concentration. The mean tumor TLI values before and after rhGH were 1.3% and 2.6% respectively; median tumor and serum IGF-I levels before rhGH were 4.64 ng/g and 63.5 ng/ml respectively; after the administration of rhGH median tumor IGF-I content was 1.8 and median serum IGF-I level was 112 ng/ml. These data suggest that, in vivo, rhGH stimulates breast cancer cell proliferation; the mitogenic stimulus is likely due to the local production of IGF-I induced by rhGH.

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Intraperitoneal infusion of recombinant human tumor necrosis factor and mitoxantrone in neoplastic ascites: a feasibility study.

In cancers limited to the abdominal cavity the intraperitoneal administration of antineoplastic drugs could be the treatment of choice because of both the limited systemic toxicity and the pharmacokinetic advantage. Preclinical studies suggest that the combination of Tumor Necrosis Factor (TNF) and mitoxantrone have a synergistic effect. On this basis, we conducted a study to verify the feasibility of the intraperitoneal administration of these drugs in patients with malignant ascites. Cohorts of three patients were treated with a fixed dose of mitoxantrone (6 mg/m2) and escalating doses of TNF (from 60 up to 200 mcg/m2), intraperitoneally, given for two hours once a week for at least four weeks. Seventeen patients with malignant ascites entered into the study. All but two patients received the planned four cycles. Sixty-six cycles were given. The most common side effects were fever (21-44% of cycles), chills (8-44%), fatigue (19-33%), loss of appetite (17-57%), malaise (25-43%), myalgia (33%), pain injection (25-83%), nausea/vomiting (33-64%). Severe fatigue, malaise and anorexia were observed only at doses of 200 mcg/m2 of TNF. Weekly intraperitoneal administration of mitoxantrone (6 mg/m2) and TNF (200 mcg/m2) is a feasible regimen with acceptable toxicity. The activity of this combination should be studied in properly designed phase II trials.

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A pilot study with cisplatin, ifosfamide and weekly administration of vinorelbine as an outpatient combination chemotherapy for advanced non small cell lung cancer.

The combination of cisplatin and ifosfamide on day 1 plus vinorelbine on day 1 and 8, every 3 weeks, has demostrated a high response rate and acceptable toxicities in advanced NSCLC patients. The present study was designed to analyse the feasibility and toxicity of a similar regimen in which vinorelbine was administered on a weekly basis in advanced NSCLC patients. The scheme consisted of cisplatin 80 mg/sqm, Ifosfamide 3 gr/sqm on day 1, Vinorelbine 25 mg/sqm on days 1,8,15, every 21 days. The dose of vinorelbine on day 8 and 15 was modified according to the absolute neutrophil count. Patients who experienced grade 3-4 neutropenia received G-CSF (300 micrograms total dose subcutaneously) from days 10 to 13 and from 17 to 20 of each subsequent course. Twelve patients were treated and forty-six courses were evaluable for toxicity. Grade 3-4 neutropenia was observed in 63% of the courses; 3 episodes of febrile neutropenia were recorded. Vinorelbine on day 15 was omitted in 52% of the courses and was given at 75% and 50% of the planned dose in 11% and 4.3% respectively; G-CSF was administered in 65.2% of the courses. This scheme is not feasible because of the high incidence of grade 3-4 neutropenia. In spite of G-CSF, the dose of vinorelbine on day 15 was omitted or reduced in the majority of the cycles.

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