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Biomedical subjects

P F Conte

Publications and source records attributed to P F Conte.

At least 91 records · Page 5Linked to original sources
PubMed1996

Paclitaxel in combination with vinorelbine in pretreated advanced breast cancer patients.

This phase II study combined paclitaxel (Taxol; Bristol Myers Squibb Company, Princeton, NJ) 135 mg/m2 by 3-hour infusion on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 (in the first 14 patients) or on days 1 and 3 (in the subsequent 20 patients). The courses were repeated every 3 weeks. The second vinorelbine dose (on days 3 or 8) was reduced or omitted according to the toxicities encountered. Thirty-four patients have been treated to date; 21 had received one prior regimen of chemotherapy, 11 had two prior regimens, and two had three prior regimens. Only two patients (6%) had not been exposed to anthracyclines. One hundred twenty-six courses have been administered: 52 with vinorelbine given on days 1 and 8, and 74 with vinorelbine administered on days 1 and 3. The most frequent toxicity was grade 4 neutropenia, which occurred in 64% of the courses; 13 episodes of febrile neutropenia have been reported in eight patients. Filgrastim was administered in 43% of the courses because of febrile neutropenia or delayed recovery (> 72 hours) from grade 4 neutropenia. Mucositis was observed in 18% of the courses (12% grade 1, 3% grade 2, and 3% grade 3). The dose of vinorelbine was reduced or omitted in 86% of courses with the days 1 and 8 schedule, and in 48% of courses with the days 1 and 3 schedule. Among 28 evaluable patients, two complete and 10 partial responses have been observed (response rate, 43%, 95% confidence interval, 19% to 51%). Median duration of response is 5+ months (range, 1 to 15 months). In conclusion, this combination is active and has acceptable toxicities in anthracycline-pretreated breast cancer patients. The delivered dose intensity of vinorelbine is higher with the schedule adopted later in the study, with vinorelbine given on days 1 and 3.

Adult↗
PubMed1996

Paclitaxel combinations as front-line and salvage chemotherapy regimens in advanced breast cancer.

Thirty-two patients with advanced breast cancer have been treated with epirubicin 90 mg/m2, immediately followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infused over 3 hours, every 21 days. The starting paclitaxel dose was 135 mg/m2, increased in subsequent triplets of patients until the maximum tolerated dose was reached at 200 mg/m2. One hundred seventy-six courses have been administered; dose-related grade 4 neutropenia was observed in 66% of the courses, with 12 episodes of febrile neutropenia. Two patients showed a decline of left ventricular ejection fraction below 50% after six courses, but no signs of congestive heart failure have been reported. The response rate is 76% (95% confidence interval, 56% to 90%), with 14% complete remissions. This level of activity is encouraging considering that 84% of the patients had failed adjuvant chemotherapy (with anthracyclines in 14 cases), and 19 had progressive disease following hormone therapy for metastasis. In another study, the toxicity and activity of a salvage regimen consisting of paclitaxel 135 mg/m2 over 3 hours plus vinorelbine 25 mg/m2 in an intravenous bolus on day 1 were evaluated; vinorelbine was given again on day 8 (in 14 patients) or on day 3 (in 20 patients), and the courses were repeated every 3 weeks. Thirty-four previously treated patients with advanced breast cancer entered the study; 20 had received one prior line of chemotherapy, II had two lines, and three patients had three lines. Thirty-two patients had been exposed to anthracyclines. Grade 4 neutropenia was observed in 64% of the courses, with 13 episodes of febrile neutropenia; four episodes of grade 3 mucositis have been reported with vinorelbine days 1 and 3. A delay in the administration of chemotherapy was necessary in 17% of the courses with vinorelbine days 1 and 8 and 16% of the courses with vinorelbine days 1 and 3; moreover, the vinorelbine dose was reduced or the drug omitted on day 8 in 86% of the courses and on day 3 in 16% of the course. An objective response was achieved in 43% of the patients. In conclusion, the combination of paclitaxel plus vinorelbine is an active salvage regimen and can be administered at greater dose intensity with the day 1 and 3 schedule.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Treatment of small hepatocellular carcinoma with percutaneous ethanol injection. Analysis of prognostic factors in 105 Western patients.

BACKGROUND: Percutaneous ethanol injection (PEI) has been used in the Far East for treating small, unresectable hepatocellular carcinoma (HCC). To clarify when treatment with PEI may be best indicated for Western patients with HCC, the authors performed a retrospective analysis of the clinicopathologic factors influencing prognosis. METHODS: From December 1987 to August 1994, 105 patients with cirrhosis with HCC received PEI as the sole anticancer treatment. Eighty-two patients had uninodular tumors smaller than 5 cm, and 23 patients had multiple lesions (2-4) smaller than or equal to 3 cm each. All patients were in Child-Pugh class A (n = 64) or B (n = 41). Survival was analyzed according to patient- and tumor-related factors by means of the Kaplan-Meier method. RESULTS: The estimated survival rates of all 105 patients were 96% at 1 year, 86% at 2 years, 68% at 3 years, 51% at 4 years, 32% at 5 years, and 24% at 6 years. Survival was not affected by sex, age, etiology of cirrhosis, or hepatitis B surface antigen or anti-hepatitis C virus positivity, but depended on Child-Pugh class (P = 0.006) and presence of ascites (P = 0.009). Patients with a pretreatment alpha-fetoprotein level of 200 ng/ml or less had a better prognosis than patients with an alpha-fetoprotein level higher than 200 ng/ml (P = 0.007). Patients with unmodular HCC of 3 cm or less had significantly better long term survival (P = 0.04) than patients with uninodular HCC of 3.1-5 cm or with multinodular tumors. Tumor grade according to Edmondson and Steiner and tumor volume, in contrast, did not significantly influence prognosis (P > 0.1). CONCLUSIONS: For Western patients with HCC treated with PEI, the prognosis was highly dependent on the severity of the underlying cirrhosis. Treatment with PEI is best indicated for patients with uninodular tumors of 3 cm or less in greatest dimension and an alpha-fetoprotein level lower than 200 ng/ml.

Administration, Cutaneous↗
PubMed1995

Suramin in patients with metastatic colorectal cancer pretreated with fluoropyrimidine-based chemotherapy. A phase II study.

BACKGROUND: The results of conventional chemotherapy in metastatic colorectal cancer are discouraging, making it a logical target for new treatment approaches a necessary consideration. Suramin is a polysulfonated naphthylurea that binds to several cellular growth factors and has in vitro activity against human colorectal cancer cells. Therefore, this Phase II study of patients with metastatic colorectal cancer was conducted to evaluate its clinical activity. METHODS: Suramin was administered as a 6-day continuous infusion every week for 8 consecutive weeks by using a computer-assisted dosing of Bayesan pharmacokinetics to maintain suramin plasma concentrations of 200-250 micrograms/ml. Twenty patients with metastatic colorectal cancer who were not responsive or in progression within 6 months after completing fluoropyrimidine-based chemotherapy entered the study. RESULTS: Toxicities included mostly Grade 1 and 2 fatigue, nausea and vomiting, peripheral neurotoxicity, creatinine elevation, and proteinuria. No objective responses were observed, but three of three patients who received 5-fluorouracil plus folinic acid after suramin achieved a partial response. CONCLUSIONS: These results indicate that suramin is inactive in patients with metastatic colorectal cancer pretreated with fluoropyrimidines. Pretreatment with suramin may have changed the biology of the tumor, sensitizing it to fluoropyrimidines. Studies to investigate this possibility are in progress.

Adult↗
PubMed1995

Long-term prognosis following macroscopic complete response at second-look laparotomy in advanced ovarian cancer patients treated with platinum-based chemotherapy. The Gruppo Oncologico Nord Ovest.

Survival (S) and progression-free survival (PFS) were evaluated in 129 advanced ovarian cancer patients, who achieved a macroscopic complete response (112 pathological complete response and 17 microscopic disease) at second-look after platinum-based combination chemotherapy with or without doxorubicin (DX). The impact on S and PFS of age, performance status (PS), stage, histology, grade (G), residual disease after first surgery (RD), chemotherapy regimen, disease status at second-look and consolidation therapy were evaluated by univariate and multivariate analysis. In the 118 months observation period, median S and PFS were 81 and 34 months, respectively. Stage, G, RD, PS and disease status at second-look had significant impact on both S and PFS in univariate analysis, whereas consolidation therapy did not influence outcome. Cox's regression analysis showed that G, RD and PS had an independent impact on PFS. Test for interaction demonstrated no statistically significant relationship between RD, chemotherapy regimen and outcome. In conclusion, advanced ovarian cancer patients with macroscopically complete remission at second-look have a substantial risk of relapse after aggressive treatment. The risk of recurrence was estimated to be maximal in the first 3 years after restaging, and was correlated with poor PS, RD > 2 cm after first surgery and undifferentiated tumour.

Adult↗
PubMed1995

Mitomycin-ifosfamide-cisplatinum (MIP) vs MIP-interferon vs cisplatinum-carboplatin in metastatic non-small-cell lung cancer: a FONICAP randomised phase II study. Italian Lung Cancer Task Force.

The FONICAP group is screening, with randomised phase II studies, the activity of new chemotherapy programmes for advanced non-small-cell lung cancer (NSCLC) looking for regimens with > 30% activity. In the present study, three regimens were tested: MIP (mitomycin 6 mg m-2, ifosfamide 3 g m-2, cisplatinum 80 mg m-2 on day 1 every 28 days); MIP-IFN (MIP and interferon alpha-2b 3 MU s.c. three times a week); and PC (cisplatinum 60 mg m-2 and carboplatin 400 mg m-2 on day 1 every 28 days). Overall 93 chemotherapy-naive patients were enrolled: 23 received MIP, 27 received MIP-IFN and 43 received PC. Eighty per cent of the patients had stage IV and 20% stage IIIb disease (positive pleural effusion or supraclavicular nodes). Response rates were as follows: MIP = 9% (95% CI 1-28%), MIP-IFN = 7% (95% CI 1-24%) and PC = 14% (95% CI 5-28%). The overall median survival was 183 days. Grade III-IV leucopenia was observed in 36% of patients treated with MIP-IFN vs 10% in the other two arms, and thrombocytopenia grade III-IV was reported in nearly 10% of patients overall. In conclusion, (1) all three regimens investigated have poor activity (< 30%); (2) when tested in multicentre randomised phase II trials, MIP displays lower activity than in phase II trials; (3) PC has similar activity to other platinum-containing regimens; (4) randomised phase II studies are a reliable and quick method of determining the anti-tumour activity of novel chemotherapeutic regimens in NSCLC.

Adult↗
PubMed1995

Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization.

PURPOSE: To compare the efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection (PEI) versus repeated TACE in the treatment of large hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-three patients with cirrhosis and a large HCC (main tumor, 3.1-8.0 cm in diameter with no more than two daughter nodules) were enrolled in a prospective, randomized study. Twenty-six patients underwent a single TACE session followed by PEI (TACE-PEI group), whereas 27 patients underwent two to five TACE sessions (TACE group). Both groups of patients were similar with regard to liver function. Follow-up ranged from 8 to 39 months. RESULTS: Complete therapeutic responses were higher (P < .05) and tumor recurrences during follow-up were lower (P < .05) in the TACE-PEI group than in the TACE group. Patients in the TACE-PEI group survived longer than those in the TACE group, although the difference was not significant (P > .1). The rates of survival without recurrence were better in the TACE-PEI group than in the TACE group (P < .05). CONCLUSION: Use of a single TACE session combined with PEI is more effective than repeated TACE in the treatment of large HCC.

Aged↗
PubMed1994

Epidoxorubicin and lonidamine in refractory or recurrent epithelial ovarian cancer.

Lonidamine (150 mg x 3 day orally, days 1-5) plus high dose epidoxorubicin (120 mg/m2 intravenously, day 3) was tested in 26 patients with refractory or recurrent epithelial ovarian cancer, to assess the anti-tumour activity and the toxicity of this combination of drugs. All patients were evaluable for toxicity and 24 for tumour response. Two complete responses (8.3%) and six partial responses (25.0%) were recorded for a total response rate of 33.3%. 6 of 8 responding patients were pretreated with anthracyclines. Stable disease was obtained in 7 patients (29.2%). Toxicity was acceptable; only 1 (3.8%) patient stopped chemotherapy because of a left ventricular ejection rate reduction > 20%. The most relevant side-effect was leucopenia (grade 3-4, 34.6%). In conclusion, the association of lonidamine and high-dose epidoxorubicin has promising activity as second-line treatment in patients with refractory or recurrent epithelial ovarian cancer.

Adult↗
PubMed1994

Tumour kinetics, response to chemotherapy and survival in primary ovarian cancer.

The analysis of thymidine labelling index (TLI) in relation to clinico-pathological variables and survival was carried out in 111 ovarian cancer patients. The significance of TLI in predicting response to aggressive first line chemotherapy regimens was examined. The overall median TLI value of 1.8% was used as a cut-off to discriminate slowly from highly proliferating cancers. 94 patients entered into two consecutive randomised trials, and were treated with six courses of cisplatin-based chemotherapy with or without doxorubicin. A significantly higher objective response of 60% was reported in the subset of patients with TLI > 1.8% as compared to 35% in patients with TLI < or = 1.8% (P = 0.03). In addition, patients achieving complete response had tumours with median TLI of 3.8% as compared to 2.4% for partial responders, 1.5% for patients with stable disease and 1.7% for those with progressive disease. A significant increase in tumour kinetics was observed in advanced cancers (P = 0.001), more undifferentiated tumours (P = 0.02) and postsurgical residual disease greater than 2 cm (P = 0.04). In univariate analysis, TLI failed to influence significantly clinical outcome: 26 versus 32 months median survival time for patients with high and low tumour TLI, respectively. In the Cox's regression model, the only independent prognostic variables were performance status and amount of residual disease after primary surgery (P = 0.000).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Synergistic antiproliferative activity of suramin and alpha 2A-interferon against human colorectal adenocarcinoma cell lines: in vitro studies.

Suramin, a polysulphonated naphthylurea proven to be an effective anticancer agent against selected tumours, and alpha 2A-interferon (alpha 2A-IFN) were investigated for their combined effects on HCT-8, HCT-15, CL-D, SW-480 and SW-620 human colorectal adenocarcinoma cell lines. All lines were sensitive to clinically achievable concentrations of suramin in a dose-dependent manner, while alpha 2A-IFN alone induced only a modest reduction of cell growth. Concomitant treatment with suramin and alpha 2A-IFN resulted in a synergistic inhibition of cell viability in each cell line at all doses tested. However, when suramin and alpha 2A-IFN were administered sequentially, inhibition of cell viability was clearly dependent on the timing of treatment schedule, with maximum effect obtained when alpha 2A-IFN was administered prior to suramin. In contrast, pretreatment with suramin was markedly inferior to the former one. In conclusion, suramin and alpha 2A-IFN exert a synergistic effect on human colorectal cell proliferation in vitro at clinically achievable concentrations. This observation may have clinical relevance although the mechanisms of interaction remain to be elucidated.

Adenocarcinoma↗
PubMed1994

Double 5-fluorouracil modulation with folinic acid and recombinant alpha-2B-interferon. A phase I-II study in metastatic colorectal cancer patients.

Twenty-two patients with metastatic colorectal cancer entered a Phase I-II trial to assess the maximum tolerable dose of alpha-2B-interferon administered intramuscularly three times per week in combination with fixed doses of 5-fluorouracil (450 mg/m2 IV for 5 days, and, from day 28, weekly) and folinic acid (200 mg/m2 IV before 5-fluorouracil) and the efficacy of this combination. Diarrhea and mucositis were the most frequent 5-fluorouracil-related toxicities and were > or = ECOG grade 3 in 23% and 18% of patients, respectively. Of 15 patients receiving interferon > or = 9 x 10(6) IU, 10 required interferon dose reduction mostly because of severe fatigue, anorexia, and declining performance status. Among 19 patients evaluable for response, 3 achieved a partial response and 1 a complete response for an overall response rate of 21% (95% confidence interval, 6-46%). In conclusion, our study demonstrates that IFN-alpha 2B at doses higher than 6 x 10(6) IU intramuscularly three times per week in the combination with 5-fluorouracil and folinic acid we used is too toxic for the majority of patients; this combination has moderate activity in metastatic colorectal cancer, although similar response rates have been reported, with less toxicity, with 5-fluorouracil plus folinic acid without IFN-alpha. A larger Phase III study would be required to determine the value of IFN-alpha in this combination.

Aged↗
PubMed1994

Delayed progression of bone metastases with pamidronate therapy in breast cancer patients: a randomized, multicenter phase III trial.

A total of 295 patients with lytic bone metastases from breast cancer were randomized to receive chemotherapy or chemotherapy plus pamidronate (Aredia) 45 mg intravenously every 3 weeks. Primary endpoints were time to progressive bone disease (evaluated by blind extramural review), and improvement in pain (according to a 6-point self-assessment scale). Secondary endpoints included incidence of bone-related complications (pathological fractures, tumor-induced hypercalcemia, need for radiotherapy), sclerotic response of lytic lesions, WHO performance status, and analgesic score. Median time to bone progression was 249 days and 168 days in the pamidronate and control groups respectively (p = 0.02). Marked improvement in bone pain was observed in 44% of patients receiving pamidronate compared to 30% in controls (p = 0.025). With respect to secondary endpoints, pamidronate reduced the need for radiotherapy (66 times vs. 82 times in controls), and median time to radiotherapy was 697 days with pamidronate, 571 in the control arm. No severe adverse reactions or worsening of chemotherapy-induced toxicities were observed during 1598 pamidronate infusions. We conclude that intravenous pamidronate is well tolerated, significantly prolongs time to progressive bone disease, and significantly improves bone pain in patients with osteolytic metastases from breast cancer.

Adult↗
PubMed1994

Therapeutic experience of the North-West Oncology Group (GONO) on ovarian carcinoma.

The North West Oncology Group is a cooperative group that has carried out several clinical trials on the treatment of ovarian carcinoma in the last 10 years. In a randomized study of advanced ovarian carcinoma patients, the combination of cisplatin plus cyclophosphamide (PC) came out as superior to cisplatin plus cyclophosphamide plus doxorubicin in terms of complete clinical and pathological response rates and 8-years progression free survival (PFS). A randomized trial showed that PAC and cyclophosphamide plus doxorubicin plus carboplatin (CAC) were equivalent in terms of objective response (OR) rates, pathologic complete response (pCR) rates, median survival (S) and median PFS. After PAC or CAC therapy, patients with pCR or minimal residual disease were included in a randomized trial comparing abdominopelvic radiotherapy (RT) versus 3 more courses of the chemotherapy they had received before. This study was stopped early because of a clear advantage in S and PFS for chemotherapy arm. Patients with macroscopic residual disease at second-look surgery and patients with progressing or relapsing disease after first line chemotherapy crossed to an alternative analogue: from PAC to carboplatin and from CAC to cisplatin. An OR was obtained in 25% of the patients of the cisplatin arm and in only 9% of the patients of carboplatin arm. Randomized clinical trials analyzing the role of intraperitoneal administration of chemotherapy and the role of biological response modifiers such as interferons in the treatment of patients with advanced epithelial ovarian carcinoma are currently ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Combination chemotherapy with vinorelbine, ifosfamide, and cisplatin: a phase II study in stage IIIB-IV non-small cell lung cancer.

Forty-five stage IIIB-IV non-small cell lung cancer (NSCLC) patients entered a phase II study designed to evaluate the toxicity and the activity of a combination chemotherapy regimen consisting of vinorelbine (25 mg/m2 days 1 and 8), ifosfamide (3 g/m2 day 1 with uroprotective mesna), and cisplatin (80 mg/m2 day 1). The regimen, VIP, was administered on an outpatient basis every 3 weeks. White blood cell counts were checked weekly, and granulocyte colony-stimulating factor was administered in case of grade 4 neutropenia lasting for more than 48 hours. Leukopenia was the most frequent toxicity, with grades 3 and 4 neutropenia reported in 25% of cycles and 11 episodes of febrile neutropenia recorded in 175 evaluable courses. The combination of vinorelbine and cisplatin did not result in additive neurotoxicity: only five patients experienced grade 2 neurotoxicity after six courses of treatment. Thirty-five patients were evaluable for response. Twenty partial responses (57%) and one complete response (2.8%) were observed, for an overall response rate of 60% (95% confidence interval, 42% to 76%). The median time to progression, measured from the start of treatment, was 7 months (range, 1 to 18+), and median survival for the whole group was 12 months (range, 1 to 18+). VIP is a well-tolerated regimen and shows interesting activity in advanced NSCLC.

Adult↗
PubMed1993

Potentiation of TNF-mediated cell killing by mitoxantrone. Relationship to DNA single-strand break formation.

Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates different cellular responses including cytotoxicity, cytostasis, proliferation, differentiation and expression of specific genes. Recent studies have demonstrated that chemotherapeutic drugs that inhibit the nuclear enzyme DNA topoisomerase II synergize with TNF in tumor cell killing in vitro and in vivo. We now report that a combination of TNF and the topoisomerase II inhibitor Mitoxantrone produced dose-dependent synergistic cytotoxicity against the human ovarian cancer cell line A2774 in a clonogenic assay (1 hr treatment). This result was obtained with simultaneous administration of the drug and the cytokine under test, and is independent of modification of Mitoxantrone uptake. This combination is responsible for an evident augmentation of "cleavable complex" formation. From isolated nuclei, we have isolated also the topoisomerase II activity; we observed an increment when the cells were previously treated with TNF, 2.5 min before nuclear extraction. After 10-30 min of treatment with TNF, the topoisomerase II activity returned to normal values. If TNF is not given with but 30 min before Mitoxantrone, no potentiation of cytotoxicity or break induction is observed. These results suggest that specific timing of the association may be needed also when attempting to translate it to animals and humans.

Cell Death↗
PubMed1993

A phase I-II study of oral doxifluridine plus radiotherapy in radiosensitive tumors of the pelvic region.

AIMS AND BACKGROUND: Fluoropyrimidines have shown synergic effects in combination with radiotherapy in several tumor types. Doxifluridine is a novel 5-fluorouracil (5-FU) prodrug which is transformed into 5-FU in neoplastic tissue. This would imply enhancement of radiotherapy by 5-FU in neoplastic tissue, where the drug is concentrated higher than in surrounding healthy tissues. METHODS: A phase I-II study was carried out on 10 patients with radiosensitive tumors of the pelvic area (4 uterine carcinomas). Escalating doses of oral doxifluridine were administered in combination with standard radiotherapy to assess the efficacy and toxicity profile of the combined treatment. The 9 evaluable patients (3 groups of 3 patients each) received oral doxifluridine, at daily doses of 500, 750, or 1000 mg, for 6 consecutive weeks in combination with a standard (1.8-2.0 Gy) dose of radiotherapy. Assessment of physical and laboratory parameters was made at baseline, then weekly up to the end of the treatment and at follow-up. RESULTS: At the final evaluation, one patient with a diagnosis of uterine carcinoma showed a complete response that lasted 10 weeks. One patient had a partial response, and 7 patients had no change. The most frequent adverse events were gastrointestinal: 27 episodes of mild to moderate nausea/vomiting and diarrhea. Three patients complained of severe diarrhea of 5-7 days duration: all patients spontaneously recovered. There were no significant changes in laboratory or clinical parameters, and no serious toxicity requiring reduction or interruption of the radiotherapy. CONCLUSIONS: The maximum tolerated dose of oral doxifluridine in combination with standard radiotherpay was assessed at 1000 mg/patient/day (equivalent to 36-38 g monthly, previously reported as mTD in phase I studies).

Administration, Oral↗