Biomedical subjects

F Pensa

Publications and source records attributed to F Pensa.

24 records · Page 2Linked to original sources

PubMed1993

The synthetic retinoid fenretinide lowers plasma insulin-like growth factor I levels in breast cancer patients.

We studied the effect of fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)], a synthetic analogue of retinoic acid, on plasma insulin-like growth factor I (IGF-I) levels in a consecutive cohort of stage I breast cancer patients belonging to a randomized phase III trial of breast cancer chemoprevention. Thirty-two women receiving 4-HPR 200 mg/daily and 28 untreated controls entered the study. IGF-I levels were determined after acid-ethanol extraction, on plasma obtained at randomization and after a mean time of 10.8 +/- 0.3 months. At baseline, there was no difference in IGF-I levels between the two groups [152.9 +/- 9.4 versus 159.2 +/- 7.0 ng/ml in treated and control group (P = 0.59), respectively]. After follow-up time, while plasma IGF-I levels were unchanged in control patients (163.3 +/- 7.4 ng/ml; P = 0.5), they were significantly reduced to 134.6 +/- 8.1 ng/ml in the patients treated with 4-HPR (P = 0.003 and P = 0.011 versus baseline and control values, respectively). Multiple regression analysis showed that treatment was the only determinant of IGF-I decline. Moreover, the interaction between treatment and age was significant, in that the decrease of IGF-I levels induced by 4-HPR administration was much more pronounced in younger patients, while an age-related decline was observed in controls. We conclude that the synthetic retinoid 4-HPR lowers circulating IGF-I levels in early breast cancer patients. Although the importance of this observation for the clinical prevention of breast cancer remains to be established, it further substantiates the rationale of the combination of 4-HPR with tamoxifen, which is known to decrease IGF-I as well and to act synergistically with the retinoid in preclinical models.

Anticarcinogenic Agents↗

PubMed1991

EGF in breast cyst fluid: relationships with intracystic androgens, estradiol and progesterone.

The relationship between intracystic levels of epidermal growth factor (EGF) and those of dehydroepiandrosterone sulphate (DHEA-S), delta-4-androstenedione (delta-4-A), 17-beta-estradiol (17-beta-E) and progesterone (PROG) have been studied in 77 breast cyst fluid (BCF) samples. EGF and all tested hormones appeared to be inversely correlated with the intracystic Na+/K+ ratio (p less than 0.001). Consequently, when the BCFs were subdivided according to the Na+/K+ ratio, significantly higher levels of EGF, DHEA-S, delta-4-A, 17-beta-E and PROG were found in Na+/K+ less than 3 BCFs compared with Na+/K+ greater than 3 BCFs (p less than 0.001 in all cases). Strong direct relationships were found among all steroid hormones when they were correlated to one another (p less than 0.001). Intracystic EGF concentration was directly and significantly correlated with each tested hormone (p less than 0.001). However, the relationship between EGF and steroid hormones appeared to be different in the 2 BCF types (Na+/K+ less than 3 or greater than 3).

Adult↗

PubMedDate not supplied

Sequential high dose-density chemotherapy in advanced ovarian cancer.

Introduction of paclitaxel or anthracyclines can improve the results of chemotherapy in advanced ovarian cancer. Dose intensification (by shortening of intervals between cycles) and sequential administration of active regimens at least theoretically may improve chemotherapy effectiveness. 18 patients entered into a pilot trial of combination chemotherapy. Treatment consisted of cisplatin 50 mg/m2, epidoxorubicin 60 mg/m2 and cyclophosphamide 500 mg/m2 every 14 days for six cycles, followed by paclitaxel 175 mg/m2 (3-hour infusion) every 14 days for four cycles. Granulocyte colony stimulating factor at 300 mcg was employed between cycles on days 5-10. 16 out of 18 patients who entered the study received a full dose chemotherapy with a ratio between actually received and planned dose intensity of 0.8 or more. No life-threatening side effect was observed and toxicity was acceptable. This new approach based on sequential administration of active regimens at high dose intensity proved feasible, active and devoid of unacceptable toxicity. The administration the booth of paclitaxel and epidoxorubicin with cisplatin and cyclophopshamide has been rendered possible. Further studies are warranted.

Adenocarcinoma, Clear Cell↗

PubMedDate not supplied

Sequential high dose-density chemotherapy with two active regimens for advanced small cell lung cancer.

16 patients with advanced small cell lung cancer were treated with a combination of cyclophosphamide (1000 mg/m2 day 1), epidoxorubicin (60 mg/m2 day 1) and vincristine (1.4 mg/m2 day 1) every 14 days for six cycles followed by a combination of cisplatin (40 mg/m2 days 1 & 2) and etoposide (100 mg/m2 days 1-3) every 14 days for four cycles. Shortening of intervals was obtained with the prophylactic employment of granulocyte colony-stimulating factor (filgrastim, 300 mcg subcutaneously from day 5 to dsy 10). In 11 patients ratio between actually delivered dose intensity and planned dose intensity of > 80% was obtained. Toxicity was acceptable and no life-threatening toxicities were observed. An objective response (partial or complete) was observed in 11 patients. The new regimen, incorporating the concepts of dose-intensification and sequential administration of regimens, is feasible and may be considered for further studies.

Aged↗

PubMedDate not supplied

A new schedule for etoposide, epidoxorubicin and cisplatin with granulocyte colony stimulating factor for advanced gastric cancer: a feasibility study.

A new polychemotherapy regimen has been developed for gastric cancer. Etoposide at the dose of 120 mg/m2 for three days, Epidoxorubicin at the dose of 30 mg/m2 on day 1 and Cisplatin at the dose of 40 mg/m2 on day 2 were administered to 26 advanced gastric patients every two weeks with the support of Granulocyte Colony Stimulating Factor from day 8 to day 12 of each cycle. The treatment was feasible with most cases (21/25) having received at least four cycles with a dose intensity > 85%, without life-threatening side effects. Toxicity was lower than that observed in the classical combinations of Etoposide-Anthracycline-Cisplatin.

Adult↗

PubMedDate not supplied

[Low-dose GM-CSF and dose intensity of antineoplastic agents].

Hematopoietic growth factors are cytokines able to modulate proliferation and differentiation of bone marrow progenitors. We have reviewed the effectiveness of GM-CSF in protecting marrow from chemotherapy-induced neutropenia, mainly in the setting of cyclic polychemotherapy; in particular, studies employing low doses of GM-CSF have been considered. G-CSF or GM-CSF may be particularly useful in situations in which the likelihood of a clinically relevant neutropenia is high, both because of higher dose intensity (obtained by intensification of doses of each cycle or by shortening of intervals between cycles) or because of pretreatment patient characteristics (old age, poor performance status, previous extensive chemotherapy or radiotherapy, experience of neutropenia in the previous cycles). GM-CSF at the conventional dose of 5 micrograms/kg was utilized to increase the etoposide dose to 900 mg/m2 in a chemotherapy program including also carboplatin and ifosfamide in patients with small cell lung cancer. In a randomized study by Ardizzoni et al., the administration of GM-CSF at the dose of 10 micrograms/kg following CEF program (cyclophosphamide, epirubicin and fluorouracil) was effective in reducing from 20 to 16 days the time interval among cycles. Since there is a relationship between GM-CSF dose levels and toxicity, it is attractive to investigate whether GM-CSF at doses lower than 5 micrograms/kg retains its myeloprotective effects, with a substantial reduction in its toxic effects. Grem et al. have observed that 3 micrograms/kg GM-CSF may allow the administration of 425 mg/m2 fluorouracil for five days; Reed et al. demonstrated that 600 mg/m2 carboplatin may be safely administered if protection with 3 micrograms/kg GM-CSF is applied; Kehoe et al. achieved acceleration of cyclophosphamide-cisplatin combination by GM-CSF at the dose of 3 micrograms/kg. We conclude that low dose GM-CSF deserves further evaluation in order to determine effectiveness and potential applications in the clinical practice.

Antineoplastic Agents↗