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Biomedical subjects

P F Conte

Publications and source records attributed to P F Conte.

At least 145 records · Page 8Linked to original sources
PubMed1987

A phase II study with danazol in metastatic breast cancer.

Danazol is a synthetic steroid that inhibits the gonadotropin secretion. Its efficacy was tested in 27 patients with metastatic breast cancer at the dose of 200 mg three times daily. Characteristics of patients were as follows. The median age was 57 years (range, 44-85). All patients were postmenopausal, and all had previously received a median of two (range, 1-3) endocrine therapies. Estrogen receptor status was known in 12 (positive in five of 12; negative in seven of 12). Dominant sites of metastases were lung in seven, bone in ten, liver in three, and soft tissue in seven. Six of 27 patients were unevaluable for response (early death, four; lost to follow-up, two). Three of 21 patients showed an objective response, eight of 21 obtained stabilization of disease, and eight progressed. The therapy was well tolerated in the majority: gastric pain was observed in three and nausea in two. Danazol could have a role in the treatment of metastatic breast cancer as an alternative regimen when other treatment has failed.

Adult↗
PubMed1987

Multimodality treatment of locally advanced breast cancer.

From 1976 to 1985, 61 consecutive patients with locally advanced breast cancer were treated with multimodality therapy. Overall 5-year survival was 30% with a median survival of 36 months. 50% of patients relapsed within 13 months. Other factors such as menopausal status, side of illness (right or left breast), responses to systemic or to local treatment, survival and progression-free survival in responders and non-responders have been analyzed.

Adult↗
PubMed1987

Conventional versus cytokinetic polychemotherapy with estrogenic recruitment in metastatic breast cancer: results of a randomized cooperative trial.

Diethylstilbestrol (DES) can induce a recruitment into the proliferative pool of previously resting breast cancer cells in vivo. In order to verify if estrogenic recruitment could result in a larger tumor cell killing by chemotherapy, 117 patients with metastatic breast cancer were randomized to receive CEF (cyclophosphamide, 600 mg/m2; epidoxorubicin, 60 mg/m2; and 5-fluorouracil, 600 mg/m2 on day 1); DES-CEF (cyclophosphamide, 600 mg/m2 on day 1; DES, 1 mg orally on days 5, 6, and 7; and epidoxorubicin, 60 mg/m2, and 5-fluorouracil, 600 mg/m2, on day 8) every 21 days. No significant difference in objective response rates, survival, or progression-free survival was seen between the two regimens. Patients in the DES-CEF arm experienced a higher complete response (CR) rate (24.1% v 16.1%), which reached statistical significance in the case of soft-tissue metastasis (48% v 27.3%; P less than .05) and estrogen receptor-negative tumors (35.7% v 11.1%; P less than .025). Survival and progression-free survival of patients refractory to treatment were not worsened by estrogenic recruitment. In the subset of patients failing after adjuvant polychemotherapy, DES-CEF unexpectedly induced a significantly longer survival (greater than 802 days v 375 days; P = .029) and progression-free survival (239 days v 192 days; P = .041) than CEF. The DES-CEF regimen was more myelotoxic, and 43.3% of the DES-CEF cycles had to be delayed because of leukopenia in comparison with 11.8% of the CEF cycles (P less than .0001). In conclusion, chemotherapy with estrogenic recruitment was able to induce more CRs in certain subsets of patients and a significant prolongation in survival and progression-free survival of patients failing after adjuvant polychemotherapy. These results have been achieved despite a significantly lower dose intensity of chemotherapy.

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↗
PubMed1987

4-Demethoxydaunorubicin (IMI-30) in refractory epithelial ovarian cancer: a pilot study.

Fifteen patients with advanced epithelial ovarian cancer were treated with 4-demethoxydaunorubicin (IMI-30) after platinum failure. A total of 33 courses of IMI-30 15 mg/m2, per os, daily for 3 consecutive days every 3 weeks were performed. Three patients experienced severe hematologic toxicity (WHO grade greater than or equal to 3), while gastroenteric toxicity was acceptable and no cardiotoxicity was observed. One minor response, 4 stabilization of disease and 7 progression were observed in 12 evaluable patients. In conclusion, IMI-30, at this scheduling, is inactive in our small series of heavily pretreated epithelial ovarian cancer patients.

Aged↗
PubMed1987

Metastatic breast cancer: an analysis of prognostic factors in patients treated with aminoglutethimide.

An analysis of 127 women with metastatic breast cancer was carried out. All patients were treated with aminoglutethimide: of 117 evaluable patients, 29 responded, 46 remained stable and 42 progressed. A series of patients' characteristics were analyzed for their prognostic importance for response to this drug. The most important features able to predict response were found to be a previous response to tamoxifen and a long disease-free survival after mastectomy.

Adult↗
PubMed1986

Survival of patients with relapsing breast cancer: analysis of 302 patients.

This retrospective study analyzes overall survival and relapse-free survival after mastectomy and survival after recurrence of 302 patients with metastatic breast cancer. In the whole group the median survival after mastectomy is 99 months: 5-year survival rate is 68.4% and 10-year survival rate is 38.5%. The median survival from relapse was 36 months: 5-year and 10-year survival rates were respectively 26.8 and 18.9%. Various subsets of patients divided according to several prognostic factors have been analyzed.

Adult↗
PubMed1986

Proliferative activity of human solid tumors evaluated by thymidine labeling index and primer-dependent alpha-DNA polymerase.

Proliferating cells, independent of their position in the cell cycle, contain a primer-dependent alpha-DNA polymerase (PDP); we have, therefore, tested the feasibility of the PDP assay in breast, ovarian, and head and neck tumors. Experimental results demonstrate that the PDP labeling index (PDP-LI) is constantly superior to the thymidine labeling index (TLI), which indicates the percentage of S phase cells. The PDP-LI/TLI ratios observed were 5.0 in breast cancer, 3.6 in ovarian cancer, and 2.5 in head and neck tumors. Higher PDP-LI scores have been obtained in metastatic breast tumor samples (PDP-LI = 8.8) compared to nonmetastatic tumors (PDP-LI = 4.9).

Adult↗
PubMed1986

A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.

Adult↗
PubMed1986

Idarubicin in advanced breast cancer: a phase II study.

Twenty-nine patients with metastatic breast cancer were treated orally with idarubicin (15 mg/m2 X 3 days every 3-4 weeks). Objective response was seen in 31% of all patients. Toxicity was acceptable. There should be further clinical trials of new anthracycline antibiotic.

Aged↗
PubMed1986

A phase II study of mitoxantrone in advanced breast cancer.

A phase II study with mitoxantrone has been carried out in 30 metastatic breast cancer patients. Of 26 evaluable patients 7 (26.9%) experienced a partial response; 7 (26.9%) patients had stable disease and 12 (46.1%) had progression. Major toxicity observed was: nausea and vomiting in 52% of patients, moderate hair loss in 53% of patients and leukopenia in 53%.

Adult↗
PubMed1986

Cytokinetic parameters of locally advanced human breast cancer treated with diethylstilbestrol and chemotherapy.

Thirty-six patients with locally advanced breast cancer received diethylstilbestrol (1 mg/die) for 3 days followed by FAC (5 Fu 600 mg/m2, adriamycin 50 mg/m2, cytoxan 600 mg/m2) on day 4, q. 21 days. After three cycles, responsive patients were submitted to surgery. Tumor kinetic parameters were evaluated by TLI and PDP-LI in 22 patients on serial tumor biopsies at diagnosis (TO), after DES (T1), 24 hrs after the first FAC (T2) and at the time of radical surgery (T3). An estrogenic recruitment was evident by TLI in 9/22 tumors and by PDP-LI in 16/22 patients. Our results demonstrate that diethylstilbestrol can induce a kinetic recruitment of breast cancer cells independently from their ER content and that chemotherapy is able to stop cell proliferation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Estrogen induced expansion of the growth fraction in receptor negative human breast cancer.

The feasibility of a cytokinetic chemotherapy based on estrogenic recruitment has been evaluated in 5 patients, affected by locally advanced breast cancer with low or absent receptor content. Tumor proliferative activity was evaluated by the thymidine labeling index (TLI) and the primer-dependent alpha DNA polymerase assay (PDP-LI) which gives an in vitro estimation of tumor growth fraction. The patients have been treated with diethylstilbestrol (DES) 1 mg/die. for 3 days, followed by FAC (5-Fluorouracil 600 mg/m2, Adriamycin 50 mg/m2, Cytoxan 600 mg/m2) i.v. on day 4 q. 21 days. Radical surgery was performed after 3 DES-FAC regimens. Tumor biopsies for evaluation of tumor proliferative activity were performed immediately before and after DES and 24 h after chemotherapy. Our results demonstrate that DES was able to induce an increase in TLI in 3/5 of the patients while the PDP-LI was significantly increased in 5/5 of the patients; subsequent chemotherapy induced a sharp decrease in tumor proliferation. These results provide the rationale for the design of cytokinetic regimens where chemotherapy is administered at the time of estrogen induced tumor cell recruitment.

Breast Neoplasms↗
PubMed1985

Cisplatin, methotrexate, and 5-fluorouracil combination chemotherapy for advanced ovarian cancer.

A combination chemotherapy including cisplatin, 25 mg/m2 on Days 1,8; methotrexate, 30 mg/m2 on Day 1; and 5-fluorouracil, 600 mg/m2 on Day 1 has been evaluated in 28 previously untreated and 10 pretreated patients with advanced ovarian cancer after debulking surgery when feasible. The pathological response rates (complete + partial responses) were 69.2 and 50% in untreated and pretreated patients, respectively. Overall 24-month survival and progression-free survival (PFS) are 19.2 and 10.9%, respectively. A significant difference in survival and PFS is evident between patients with less and more than 2 cm residual disease and between responders (CR + PR) versus nonresponders. No renal toxicity was induced and no cycles had to be delayed because of hemathologic toxicity.

Adenocarcinoma↗
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↗
PubMed1985

Chemotherapy following estrogen-induced expansion of the growth fraction of human breast cancer.

We have evaluated the feasibility of a cytokinetically oriented regimen based on the induction of cell recruitment by diethylstilbestrol (DES) in locally advanced human breast cancer. Tumor proliferative activity was evaluated by the thymidine labeling index and the primer-dependent alpha-DNA polymerase labeling index, which gives an in vitro estimation of the growth fraction. Sixteen previously untreated patients received DES (1 mg daily for 3 days) followed by FAC [5-fluorouracil (600 mg/m2): Adriamycin (50 mg/m2): Cytoxan (600 mg/m2)] i.v. on day 4 every 21 days. Radical surgery was delayed to allow for three DES-FAC regimens in responsive patients. Proliferative activity on tumor biopsies was evaluated immediately before and after treatment with DES, 24 h after chemotherapy and, in nine patients, at the time of radical surgery. DES was able to induce a significant increase in thymidine labeling index in 8 of 16 patients, while the primer-dependent alpha-DNA polymerase labeling index was significantly increased in 13 of 16 tumors, independently of their estrogen receptor content. Subsequently administered chemotherapy induced an early decrease in tumor proliferation. In the nine patients submitted to surgery after three DES plus FAC courses, the average thymidine labeling index and primer-dependent alpha-DNA polymerase labeling index were 27.8 and 73% of the pretreatment values. Our preliminary results provide the rationale for the design of new therapeutic schemes in which antitumor drugs are given at the time of estrogen-induced tumor cell recruitment. Further extended studies are required to establish whether induction of tumor cell recruitment will actually translate into appreciable improvement of the clinical response to chemotherapy.

Adult↗
PubMed1985

Regional intra-arterial chemotherapy of metastatic liver cancer.

The rationale of regional intra-arterial chemotherapy of metastatic liver cancer is based on the possibility of providing higher levels and longer exposure time of the tumor to drugs. The recent availability of a totally implantable portable pump (Infusaid) had greatly reduced the catheter-related complications with very good patient compliance. An extensive review of the published results in colorectal carcinoma does not allow us to reach any firm conclusion on the validity of regional treatment: many authors report high response rates and satisfactory long term control of liver disease, but impact on survival is questionable because of extrahepatic tumor progression. Prospective randomized trials comparing systemic versus regional plus systemic chemotherapy are needed. Finally, our personal experience in colorectal and breast cancer is presented.

Adult↗