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Biomedical subjects

P F Conte

Publications and source records attributed to P F Conte.

At least 109 records · Page 6Linked to original sources
PubMed1993

Alpha-2B-interferon plus floxuridine in metastatic renal cell carcinoma. A phase I-II study.

BACKGROUND: Both alpha-interferon and floxuridine are active in metastatic renal cell carcinoma (MRCC); the two agents have demonstrated antitumor synergism and different clinical toxicities. The purpose of this study was to determine the maximum tolerable dose (MTD) of floxuridine (FUDR), administered as a constant continuous infusion for 14 days every 28 days, in combination with fixed doses of alpha-2B-interferon and to preliminarily evaluate the antitumor activity of this combination. METHODS: Sixteen patients entered the study; six had previously received alpha-interferon. Alpha-2B-interferon was administered at the dose of 10 x 10(6) IU intramuscularly 3 times/week and floxuridine at the starting daily dose of 0.075 mg/kg. This dose was escalated at each subsequent cycle up to dose-limiting toxicity. RESULTS: Most common toxicities included fever and flue-like symptoms, fatigue, anorexia, diarrhea, mucositis, and nausea, and 55% of patients experienced greater than or equal to Grade 2 toxicity, mostly diarrhea, for floxuridine doses greater than 0.125 mg/kg/d. Among 15 evaluable patients, 1 achieved a complete response and 4 achieved a partial one (33%; 95% confidence interval, 12-62%). Three partial responses were obtained in patients pretreated with alpha-interferon plus vinblastine. CONCLUSIONS: The combination of alpha-2B-interferon and floxuridine is feasible, and in our regimen the recommended daily dose of floxuridine for Phase II studies was 0.125 mg/kg. This combination is active in metastatic renal carcinoma, but further studies are needed to determine whether alpha-2B-interferon has added anything to the FUDR infusion or vice versa.

Adult↗
PubMed1993

The impact of received dose intensity on the outcome of advanced ovarian cancer.

It has been demonstrated that the prognosis of ovarian cancer is influenced by the dose intensity of cytotoxic treatment. The impact of received dose intensity of platinum-based combination chemotherapy on disease outcome was analysed in 226 stage III-IV ovarian cancer patients entered into two prospective randomised trials. All patients received either cisplatin or carboplatin and cyclophosphamide with or without doxorubicin for six courses after primary surgery. The impact of the received dose intensity of each drug (RDI), the average received dose intensity of the treatment regimen (ARDI) and the relative total drug dose (RTD) on progression-free survival (PFS) and survival were analysed. In the 198 patients receiving the full six courses of treatment, RDI of cisplatin or carboplatin, ARDI and RTD were > 0.76 in 74.2, 61.1 and 65.1% of cases, respectively. Although the differences were not significant, pathological complete response was more frequently observed in the group of patients with ARDI < 0.75, whereas the partial response rate was higher in the ARDI > or = 0.76 group. Median survival and PFS were 19 and 13 months; 22 and 10 months; 23 and 13 months for the groups of patients receiving chemotherapy at a ARDI of < 0.75, > or = 0.76-0.99 and > 1.00, respectively (P = not significant). It appears that modest dose modifications and brief treatment delays during first-line platinum-based chemotherapy do not affect response rate, survival and PFS in advanced ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Advanced epithelial ovarian cancer: 1993 consensus statements.

BACKGROUND: Over the last few days of a 5-day international workshop held in June 1993, a group of specialists in the field of advanced epithelial ovarian cancer tried to reach consensus on a number of issues with implications for standard practice and for research. METHODS: Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, management recommendations, dose intensity, supportive care, drug resistance, second-line treatment, investigational drugs, and tumour markers. Discussing the management recommendations, the group attempted to arrive at answers to four questions: Is there in fact a cure rate for advanced ovarian carcinoma? Are there prognostic factors which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? In a plenary meeting these issues were discussed. RESULTS: Consensus statements were achieved on all topics mentioned above. This article reports on the statements written by the chairmen and approved by the consensus group.

Antineoplastic Agents↗
PubMed1993

Role of anthracyclines in first line combination chemotherapy of ovarian carcinoma.

The association of cisplatin plus cyclophosphamide (PC) is considered to be the standard medical treatment for advanced ovarian carcinoma, while the role of doxorubicin in combination with cisplatin and cyclophosphamide (PAC regimen) is still controversial. Recently, four randomized clinical trials evaluating PC versus PAC regimen have been published. None of these studies showed a convincing advantage for the addition of doxorubicin to PC. By pooling the data from the 1200 or so patients included in these four studies and analyzing them with the statistical technique of meta-analysis, a statistical benefit for PAC over PC is demonstrated in terms of pathologic complete response rate (30 vs 23%, P = 0.01) and 6-year survival rate (27 vs 21%, P = 0.01).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Advanced ovarian cancer. Carboplatin versus cisplatin.

BACKGROUND: Since the introduction of the second generation platinum compound carboplatin, debate has taken place about whether this analogue can replace cisplatin in combination chemotherapy regimens for the treatment of ovarian cancer patients. MATERIALS AND METHODS: In the present review the pharmacologic characteristics of carboplatin and cisplatin and the results of comparative studies are described. RESULTS: Many of the trials performed comparing carboplatin with cisplatin, either as single agent first-line therapy or in combination chemotherapy suggest equivalent results. However, most of these trials are characterized by an inadequate patient number to detect small but important differences, inadequate carboplatin doses, ratios < 4:1, and crossover to the other analogue which makes survival comparisons difficult. Superior results in terms of either progression-free survival or overall survival have been obtained with cisplatin in two larger randomized studies of combination chemotherapy. Furthermore, another randomized study indicates substantial differences in favour of cisplatin in the subgroup of patients with < 1 cm residual tumour. Generally, there is a lack of long-term follow up. CONCLUSIONS: Based on the presently available data it is recommended that carboplatin should not routinely replace cisplatin in the management of patients with potentially curable small volume disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Prediction of survival by thymidine labelling index in patients with resistant ovarian carcinoma.

The relationship between tumour proliferative activity, evaluated by thymidine labelling index (TLI), clinicopathological variables and clinical outcome, was analysed in a series of 64 chemotherapy-resistant, ovarian cancer patients. The median TLI of 4.6% (range 0.01-45.7) was used as the cut-off to discriminate rapidly from slowly proliferating tumours. Univariate analyses showed a significant advantage in survival for patients with TLI less than or equal to 4.6 (P = 0.0004), ECOG performance status less than or equal to 1 (P = 0.0001) and residual disease after primary surgery less than or equal to 2 cm (P = 0.019). Multivariate analysis demonstrated that performance status was the only independent prognostic variable, although TLI was the last covariate removed from the Cox's regression model.

Carcinoma↗
PubMed1992

Cisplatin-based combination chemotherapy with or without doxorubicin in advanced epithelial ovarian cancer: 8-year update of a randomized multicentric clinical trial. The Gruppo Oncologico Nord Ovest (GONO).

One hundred and twenty-five patients with advanced epithelial ovarian cancer (EOC) were postsurgically included in a multicentric clinical trial comparing the association of cisplatin (CDDP) (50 mg/m2 iv day1) + cyclophosphamide (CTX) (600 mg/m2 iv day 1) (PC regimen) versus the combination of PC + doxorubicin (ADM) (45 mg/m2 iv day 1) (PAC regimen), repeated every four weeks. After the sixth course of chemotherapy, patients without clinical evidence of disease or with surgically resectable residual disease (RD) underwent second-look laparotomy. Afterwards patients in surgical complete response (sCR) stopped chemotherapy, while partial responders or patients with stable disease received six more courses of the same regimen used as first-line treatment. Among the 67 patients with measurable RD, PAC regimen achieved a better clinical complete response (40.6% vs 20.0%); the difference approached statistical significance. In the 75 patients who underwent second-look laparotomy, PAC regimen induced a significantly higher sCR rate (62.2% vs 39.5%, p less than 0.05). The median survival (S) and progression free survival (PFS) were better in PAC arm, even if the differences were not statistically significant. Eight-year S and 8-year PFS were 32.7% and 24.7% respectively, for PAC arm, and 23.9% and 14.1%, respectively, for PC arm. These data seem to confirm the clinical advantage provided by the addition of ADM to PC regimen in the treatment of advanced EOC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Effect of recombinant human tumor necrosis factor on A2774 human ovarian cancer cell line: potentiation of mitoxantrone cytotoxicity.

Recombinant human tumor necrosis factor (rHuTNF) is a macrophage-secretory protein with antitumor activity. In vivo and in vitro cytotoxicity studies have been carried out to test the effectiveness of rHuTNF alone or in combination with chemotherapeutic agents. We have evaluated the direct cytotoxic effect of rHuTNF on a human epithelial ovarian cancer cell line in vitro (A2774), alone, or in combination with mitoxantrone (Mit), a topoisomerase II (Topo II) targeted drug. Our results not only suggest that rHuTNF is directly cytotoxic, but also that it is able to induce a very strong potentiation of Mit cytotoxicity.

Dose-Response Relationship, Drug↗
PubMed1991

Abdominopelvic radiotherapy following surgery and chemotherapy in advanced ovarian cancer.

Thirty advanced ovarian cancer patients have been treated with sequential multimodality treatment including primary surgery, cisplatin or carboplatin-based polichemotherapy, second-look laparotomy followed by abdominopelvic irradiation (moving strip or open-field technique). Toxicity related to the combined treatment was acceptable: only three patients failed to complete and two patients delayed the prescribed course of radiotherapy because of acute myelosuppression or gastroenteric disturbances. One patient without evidence of disease required laparotomy for bowel obstruction one month after completion of radiotherapy. No other chronic toxicity of clinical significance has been observed. Actuarial three-year survival significantly correlated with residual disease at the start of radiotherapy: no residuum, 100%, microscopic disease, 52%; less than 2 cm macroscopic disease, 27.4% (P less than 0.05), whereas recurrences were less frequent only in the group of pathological complete responders (3/9) compared to patients with limited disease (6/11 with micro and 7/10 with macroscopic residuum). In conclusion radiotherapy following surgery and chemotherapy is not associated to serious morbidity but its value in improving progression-free survival rates has to be tested in randomized trials.

Abdomen↗
PubMed1991

Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.

One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.

Adult↗
PubMed1990

In vivo manipulation of human breast cancer growth by estrogens and growth hormone: kinetic and clinical results.

Since 1983, a series of experimental and clinical studies have been carried out on the possibility of enhancing the chemotherapy effectiveness in breast cancer by expanding the fraction of cycling cells. Theoretically estrogens should recruit breast cancer cells and this fact should result in a higher killing efficiency of antiproliferative drugs. Actually it has been clearly shown, by means of the thymidine labeling index and primer-dependent alpha-DNA polymerase assay, that low doses of diethylstilbesterol are able to increase the tumor proliferative activity of human breast cancer in vivo (estrogenic recruitment). Three randomized trials have been carried out (one in locally advanced and two in metastatic breast cancer) comparing conventional polychemotherapy vs chemotherapy with estrogenic recruitment. Only limited advantages have been observed in these trials. Searching for new modalities of kinetic manipulation of tumors, recombinant human growth hormone has been employed in a pilot study: the preliminary results indicate that it largely enhances tumor proliferative activity, suggesting the possibility of employing a growth factor system to increase chemosensitivity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Prognostic factors in stage IV ovarian carcinoma treated with platinum-based regimens.

Eight factors were analyzed for prognostic significance in univariate analyses in a series of 76 women with stage IV ovarian carcinoma treated with combination chemotherapies including cisplatin or carboplatin. The clinical objective and pathologic complete response rates were 51.2% and 27.3%, respectively. Median overall survival and progression-free survival were 15 and 7 months, respectively. No variables reached statistical significance. Trends toward better survival were noted for grades 1 and 2 for the adriamycin-containing regimen. Using progression-free survival as an end point, significant prognostic factors included complete clinical or pathologic response. Our data confirm that the standard approach is unlikely to modify the clinical outcome of stage IV ovarian cancer. New treatment modalities including high-dose-intensity regimens and neo-adjuvant chemotherapy delivered before surgery could improve clinical results. Moreover, biologic characterization of ovarian tumors may provide information to design specifically targeted treatment.

Adult↗
PubMed1990

[Neurotoxicity of intra-arterial cis-platinum (CDDP) in the locoregional treatment of diffuse liver metastasis of carcinoma of the colon and rectum].

Peripheral neurotoxicity of i.v. cisplatin (CDDP) at high cumulative dosage is well documented. On the contrary neurotoxicity of CDDP following intra-arterial administration is less known. Five patients with liver metastasis from colorectal carcinoma have been treated with intraarterial CDDP and i.v. 5-fluorouracil according to a trial of the National Registry on Implantable Devices (RNSI); in these patients a severe peripheral neurotoxicity has been observed since the fourth cycle of chemotherapy. In the present paper we report the electroneurographic changes observed immediately after chemotherapy and several months later. Clinical characteristics of neuropathy following i.a. CDDP are the following: preferentially localized at the distal extremities of the limbs, exclusively sensitive, not reversible.

Adult↗
PubMed1990

Megestrol acetate: phase II study of a single daily administration in advanced breast cancer.

A new formulation of megestrol acetate, a semisynthetic oral progestin used in the hormonal treatment of breast cancer, allows the administration of 160 mg of the drug in a single daily dose. Sixty-nine postmenopausal patients with advanced breast cancer have been treated with this regimen: five patients received megestrol acetate as first-line treatment of their metastatic disease, while all the others had been previously treated with one or more regimens of chemotherapy and/or hormone therapy. The median duration of the treatment for evaluable patients was 3 months (range 1-13+). Among 65 evaluable patients 2 complete responses and 12 partial responses (objective response rate 21.5%; 95% confidence limits 12.31%-33.49%) were observed. Median duration of response was 7 months (range 2-12+). Responses were observed both in visceral and in non-visceral sites of disease. Twenty-nine patients obtained a stabilization of disease (44.7%), and twenty-two progressed (33.8%). Median duration of stabilization was 4 months (range 3-13+). Median survival for all patients from the start of megestrol acetate was 9 months (range 1-22+). The most common side effect of therapy was weight gain, occurring in 36% of patients. Megestrol acetate on a single-daily-dose schedule can be considered as an interesting hormonal treatment for advanced breast cancer, especially in the clinical instance of patients who, after having obtained a remission or stabilization of disease with tamoxifen, need further palliative treatment.

Body Weight↗
PubMed1990

Chemotherapy versus radiotherapy in the management of ovarian cancer patients with pathological complete response or minimal residual disease at second look.

The management of patients with epithelial ovarian cancer with no or minimal residual disease at second-look laparotomy after aggressive surgery and platinum-based chemotherapy has not been definitively established. We report the results of a randomized study comparing three more courses of the same chemotherapy inducing the response (21 patients) with whole-abdomen radiotherapy (20 patients). Thirty-eight patients responded to first-line chemotherapy and three had stabilization of disease. In eight patients tumor debulking was performed at second-look laparotomy. No severe toxic effects were noted in both arms. Bowel obstruction occurred in one patient treated with radiotherapy. At a median follow-up of 22 months, 11 of 20 patients in the radiotherapy arm and 6 of 21 in the chemotherapy arm progressed and 9 and 3 patients died, respectively. Although the number of randomized patients is small we stopped the trial because of the survival and progression-free survival advantage of chemotherapy-treated patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Crossover study with cisplatin or carboplatin in advanced ovarian cancer.

Fifty-seven patients who had progressed during or relapsed after randomized first-line combination chemotherapy containing cisplatin or carboplatin were entered into a crossover study in which the analog not previously assigned was administered alone as salvage treatment. Carboplatin and cisplatin were administered at doses of 400 and 100 mg/m2, respectively, every 28 days. Among the 24 patients enrolled in the cisplatin arm, 6 (25%) objective responses (ORs) (3 complete, 3 partial) were observed, whereas 3 partial responses were obtained in the 33 carboplatin-treated patient (9%). Analysis of results, according to response to first-line chemotherapy, demonstrated that the patients who progressed were sensitive only to cisplatin second-line treatment (OR: 3/12), with no responders among carboplatin-treated patients (OR: 0/11). All patients were treated on an outpatient basis and therapy-related toxic effects were mild, consisting chiefly of myelosuppression, and more frequent in the carboplatin group. In our opinion, carboplatin 400 mg/m2 per cycle is scarcely effective in patients with refractory or relapsed ovarian cancer pretreated with cisplatin regimens, whereas cisplatin 100 mg/m2 per cycle appears to be an effective salvage therapy even in patients not responding to carboplatin. The dose of carboplatin should be further escalated especially in refractory patients.

Carboplatin↗