Biomedical subjects

A Fornasiero

Publications and source records attributed to A Fornasiero.

At least 19 recordsLinked to original sources

PubMed2003

Ifosfamide in thymic neoplasms.

The role of systemic chemotherapy and optimal regimen in thymic neoplasms remains uncertain, because they are rare mediastinal tumors, frequently encapsulated or noninvasive at the time of presentation and surgical excision is adequate treatment. Chemotherapy is an essential treatment modality in advanced or recurrent disease and an increased number of publications on this aspect of management has appeared in the last 10 years. Both single-agent and combination chemotherapy have demonstrated activity in the adjuvant and neoadjuvant settings. There are little data concerning the activity of ifosfamide in thymoma and further investigation of the role of this drug in combination chemotherapy regimens, particularly as an alternative to the inclusion of cyclophosphamide, is warranted.

Antineoplastic Agents, Alkylating↗

PubMed1999

Preoperative combined radiotherapy and chemotherapy for rectal cancer does not affect early postoperative morbidity and mortality in low anterior resection.

PURPOSE: It is not yet known whether preoperative combined radiotherapy and chemotherapy for rectal cancer affects postoperative mortality and morbidity. We therefore evaluated early postoperative complications in patients given adjuvant radiotherapy and chemotherapy before surgery for middle and lower rectal adenocarcinoma. METHODS: Between 1994 and 1998, 41 patients underwent combined preoperative pelvic radiotherapy and chemotherapy at our institution. Most of the patients had 45 Gy (1.8 Gy/day/25 fractions) during five weeks plus 5-fluorouracil (350 mg/m2/day) and low-dose leucovorin (10 mg/m2/day) bolus on Days 1 to 5 and 29 to 33. Surgery was performed four to six weeks after completion of adjuvant therapy. The 41 patients (Group A) were retrospectively compared with 30 patients (Group B) who, in the same period, underwent surgery without preoperative adjuvant therapy. The groups were homogeneous for age, gender, preoperative risk factors, operating surgeon, and pathologic stage. Mean distance of the tumor from the anal verge was shorter in Group A patients (P = 0.031). RESULTS: There were seven major postoperative complications in each group. No significant differences were found between the groups for morbidity and mortality rates. Considering all patients, more postoperative complications were found in patients scored as American Society of Anesthesiologists 3, in those with a preoperative hemoglobin value < 10 g/dl, and in those without a diverting stoma (P = 0.0048, P = 0.0453, and P = 0.0033, respectively). At multivariate analysis, independent predictors of major complications were American Society of Anesthesiologists score (relative risk, 343; P = 0.022), diverting stoma (relative risk, 159; P = 0.010), type of surgical procedure (relative risk, 38.9; P = 0.048), preoperative hemoglobin value (relative risk, 9.72; P = 0.061), and intraoperative blood loss (relative risk, 1; P = 0.027). In Group A patients, the absence of diverting stomas was associated with major postoperative complications (P = 0.0307), and independent predictors of major complications were American Society of Anesthesiologists score (relative risk, 56; P = 0.111) and absence of a diverting stoma (relative risk, 22.42; P = 0.222). CONCLUSION: Early postoperative complications after resection for middle and lower rectal adenocarcinoma are affected by intraoperative and preoperative risk factors and absence diverting stomas, but not by preoperative adjuvant therapy.

Adenocarcinoma↗

PubMed1998

Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate.

PURPOSE: To compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: Five hundred fifty-one patients with locally advanced, locoregionally recurrent or metastatic breast cancer were randomly assigned to receive letrozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were analyzed for tumor response and safety variables up to 33 months of follow-up evaluation and for survival up to 45 months. RESULTS: Letrozole 2.5 mg produced a significantly higher overall objective response rate (24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significantly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively). For time to progression, letrozole 2.5 mg was superior to letrozole 0.5 mg (P = .02), but not to MA (P = .07). There was a significant dose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain. CONCLUSION: The data show letrozole 2.5 mg once daily to be more effective and better tolerated than MA in the treatment of postmenopausal women with advanced breast cancer previously treated with antiestrogens.

Administration, Oral↗

PubMed1995

Prognostic factors in resectable gastric cancer: results of EORTC study no. 40813 on FAM adjuvant chemotherapy.

BACKGROUND: The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment. METHODS: In a randomized clinical trial on adjuvant FAM2 chemotherapy, quality of surgery was evaluated by comparing surgical and pathology data. Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients, tumor, and therapy. RESULTS: Of 314 patients randomized from 28 European institutions, 159 comprised the control and 155 the FAM2 group. After a median follow-up of 80 months, no statistically significant difference was found between survivals. However, for recurrence time, treated patients had a significant advantage over controls (p = 0.02). At univariate analysis, statistically significant differences in survival and time to progression emerged for T, N, disease stage and "adequacy" of surgery. The multivariate analysis retained preoperative Hb level, T, N, and "adequacy" of surgery for time of survival; and T, N, "adequacy" of surgery and adjuvant chemotherapy for recurrence time. CONCLUSIONS: Disease stage is the most important prognostic factor. "Adequate" surgery has an important effect. Adjuvant FAM2 delayed time of recurrence, but did not influence overall survival.

Adenocarcinoma↗

PubMed1995

Combination goserelin and tamoxifen therapy in premenopausal advanced breast cancer: a multicentre study by the ITMO group. Italian Trials in Medical Oncology.

It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer.

Adult↗

PubMed1994

Phase II study on neoadjuvant hyperthermic-antiblastic perfusion with doxorubicin in patients with intermediate or high grade limb sarcomas.

BACKGROUND: Locoregional control of soft tissue sarcomas of the limbs is achieved generally using a multidisciplinary approach consisting of conservative surgery combined with radiation therapy, intraarterial chemotherapy, or hyperthermic antiblastic perfusion (HAP). Before surgery, HAP seems to be the more suitable tool in decreasing tumor mass and allowing limb-sparing surgery. The authors' aim was to ascertain the activity of HAP with doxorubicin against intermediate or high grade limb tumors. METHODS: In 23 patients with limb sarcomas (2 patients International Union Against Cancer Stage IIA, 4 stage IIB, 1 stage IIIA, 11 stage IIIB, and 5 stage IVB) doxorubicin was administered via HAP 4-6 weeks before surgery. The drug (bolus, 0.7-1.4 mg/kg) was perfused for 60 minutes with a tumor temperature of at least 40.5 degrees C (range, 40.5-42.6 degrees). Tumor necrosis was then assessed radiologically and pathologically. RESULTS: Systemic toxicity was hematologic grade (G) 2 in 2 patients, gastrointestinal (hepatic) in 6, G1 in 2, G2 in 3, and G3 in 1; 2 patients had alopecia; locoregional toxicity (graded according to Wieberdink) was G1 or G2 in 18, G3 in 4, and G4 in 1. Tumor necrosis was more than 50% in 17 patients (74%). Limb-sparing surgery was feasible in 20 patients (91%). At present, 14 patients are alive. Six had local recurrences, and eight had distant metastases. CONCLUSIONS: Our findings show that HAP with doxorubicin is an active and well-tolerated procedure within a multidisciplinary approach to treatment of limb sarcomas.

Adult↗

PubMed1993

Chemotherapy and operation for invasive thymoma.

Sixteen patients with invasive thymoma (stage III and stage IVA) were treated with chemotherapy and then operation. All tumors were considered nonresectable after first staging, and patients were treated with the following chemotherapy in 4-day courses, administered intravenously: cisplatin (50 mg/m2) and doxorubicin (40 mg/m2) on day 1, vincristine (0.6 mg/m2) on day 3, and cyclophosphamide (700 mg/m2) on day 4. The courses were repeated every 3 weeks, and toxic effects were well tolerated. Seven patients (43%) had a complete remission, and nine patients (57%) had a partial remission, with an overall complete remission plus partial remission rate of 100%. After chemotherapy all patients underwent operation. We performed 12 sternotomies and four posterolateral thoracotomies. At operation 11 patients had radical resection and five had partial resection. We administered radiotherapy in 11 patients who had histologically demonstrated tumor after operation. In five patients, the specimen showed only fibrosis; these patients received three cycles of chemotherapy but not radiotherapy. Median survival was 66 months with a 3-year survival of 70%. We believe that neoadjuvant chemotherapy with surgical intervention is justified for advanced invasive thymoma; a longer follow-up and a larger number of patients will determine the impact of this treatment on long-term survival.

Adult↗

PubMed1992

Deflazacort and fluoximesterone in advanced, pretreated breast cancer.

A very simple, low dose, orally administered regime (10 to 15 mg of fluoximesterone + 6 mg of deflazacort daily for periods of 1 to several months) resulting in mild-acceptable toxicity (essentially some weight gain) determined subjective improvement in 2/3 of 34 evaluable patients (out of 36 treated) and an objective measurable tumor reduction in 1/3, although most patients had been previously treated with chemotherapy and hormone treatment and proved primarily or secondarily refractory. The receptor status at the beginning of fluoximesterone+deflazacort treatment was not known, except in one negative-receptor patient, who responded to the combination after becoming resistant to tamoxifen (see photo). In some patients the condition of hormone refractoriness would suggest a no-treatment policy, but a trial with this regime is always convenient as it may improve both duration and quality of life.

Adult↗

PubMed1992

Prospective controlled trial with antiestrogen drug tamoxifen in patients with unresectable hepatocellular carcinoma.

Clinical and experimental evidence indicates that estrogens are involved in the control of hepatocyte proliferation both in normal and in neoplastic conditions. Thirty-two cirrhotic patients with unresectable or otherwise untreatable hepatocellular carcinoma were allocated to receive either tamoxifen (30 mg/day) or no treatment. The patients in the two groups were matched for age, male/female ratio, Child-Pugh class, approximate tumor volume (US and CT scan), and etiology of the underlying cirrhosis. Survival of the tamoxifen-treated patients (life-table, Wilcoxon-Breslow) was significantly prolonged (P = 0.0038), with 35% (vs 0%) survival at 12 months. No difference was observed between males and females or between alcoholic and nonalcoholic cirrhosis. In 40% of tamoxifen-treated patients, the levels of alpha-fetoprotein declined. In conclusion, the antiestrogen tamoxifen appears to be effective in the palliative treatment of hepatocellular carcinoma. An initial decline in alpha-fetoprotein levels may represent an early favorable prognostic sign.

Aged↗

PubMed1992

Extramedullary plasmacytoma: clinical behaviour and response to treatment.

The clinical features and response to treatment of 35 patients (pts) with extramedullary plasmacytoma (EMP) were retrospectively analysed. The median age at diagnosis was 49 years (28-72). Twenty-two pts (63%) had stage I disease (localized to the primary site) 12 of whom (34%) had stage I-E (locally extended). Three pts (9%) had stage II (regional lymph nodes involved) and 10 (29%) stage III (disseminated disease). In locoregional disease (stages I, I-E, II) complete local control was achieved in 22 of 25 pts (88%), while in diffuse disease (stage III) complete remission (CR) was obtained in 5 of 10 pts (50%) (p = 0.05). In 9 of 18 pts treated with surgery, local control was achieved, and in 8 of the 9 patients with incomplete resection local control was obtained with additional radiation and/or chemotherapy. In 8 (66%) of the 12 pts treated with radiation complete local control was achieved. In 11 (58%) of 19 pts evaluable for initial chemotherapy CR was obtained. Three of these pts were treated with chemotherapy only and were alive and disease-free after a minimum follow-up of 8 years. The median time to relapse in local disease was 48 months versus 13 in disseminated disease. For pts with local disease the median survival time was 114 months and for disseminated disease 16 months (p = 0.0000). We conclude that in stage I chemotherapy is curative per se. In local stages (I, I-E and II) adjuvant chemotherapy should be considered, while in stage III only palliative therapy is feasible.

Adult↗

PubMed1991

Chemotherapy for invasive thymoma. A 13-year experience.

From 1977 to 1990, 37 patients with Stage III or IV invasive thymoma (20 men and 17 women; median age, 40 years of age) were referred for chemotherapy to the Padova Medical Oncology Department. All patients initially received the same regimen (50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (IV) on day 1, 0.6 mg/m2 of vincristine IV on day 3, and 700 mg/m2 of cyclophosphamide IV on day 4 [ADOC]), recycling at monthly intervals. No life-threatening side effects were noted. The overall clinical response rate (complete response plus partial response) was 91.8%, with 43% complete remissions. Median duration of response and survival were 12 months (range, 2 to 96+ months) and 15 months (range, 5 to 96+ months), respectively. Seven of the 16 complete remissions were pathologically confirmed at subsequent thoracotomy. Other chemotherapy combinations and radiation therapy have been applied as second-line treatment, achieving only minimal responses. In the opinion of the authors, such chemotherapy deserves evaluation for adjuvant and neo-adjuvant treatment of invasive (and/or inoperable) thymoma due to the high complete response rate and overall response rate.

Adult↗

PubMed1991

Adjuvant treatment for gastric cancer.

In spite of progress made in surgical techniques and intensive care, only a slight improvement in the therapeutic control of gastric carcinoma has been achieved in the last 20 years. In this paper we present a review of controlled clinical trials on adjuvant chemotherapy and chemo-immunotherapy for gastric cancer and this topic is discussed in the light of our experience and that of the Gastrointestinal Group of the European Organization for Research and Treatment of Cancer. The results of adjuvant therapy are less satisfactory in Western countries than in Japan. The efficacy of the 5-fluorouracil + adriamycin + mitomycin C regimen in advanced gastric cancer has not been confirmed in an adjuvant setting. The therapeutic benefit reported in Japanese studies may be due to a chemotherapy started intraoperatively or during the immediate postoperative period and should also be considered in the light of a standardized surgical treatment. The new therapeutic trends, using recent chemotherapeutic associations tested in Phase I and II clinical trials or combining traditional chemotherapy with different types of immunostimulators, are discussed. Only when large-scale clinical studies have been made will it be possible to confirm their therapeutic efficacy.

Antineoplastic Agents↗

PubMed1991

[Neoplasms of the gallbladder and the extrahepatic bile ducts: radio-chemotherapeutic combined treatment. Results in 18 treated cases].

According to current literature, the main cause of death in patients with gallbladder (GB) and extrahepatic biliary ducts (EHBD) neoplasms is related to local and locoregional tumor spread rather than to distant metastases. Surgery, even when radical, is followed by a high number of relapses. That is why postoperative radiation therapy (RT) is usually combined with surgery. Alone, however, RT is not effective enough to markedly improve loco-regional control, considering that the adjacent organs would be damaged by higher doses. Referring to experimental studies published in the 1960s and relative to the biological effect of ionizing radiation with 5-Fluorouracil (5-FU) in slowing the pace of tumor growth, the Department of Radiotherapy, together with the Department of Medical Oncology in Padua General Hospital, began administering a combined surgical-chemo-radiotherapeutic protocol in January 1982, to January 1989. The protocol included 5-FU administration both 3 days before and during RT, after a surgical intervention as radical as possible. Eighteen patients were given this treatment. By the end of December 1989, 7 patients were alive--6 of them disease-free with a 26-month mean survival. Eleven patients died--7 due to local/loco-regional relapse, 1 from a distant metastasis, 1 from gastric hemorrhage, with no disease, and 2 from unknown causes. Overall mean survival in the two groups was 16 months. The combined treatment proved to be tolerable and feasible, even though severe complications were observed in 2 patients, 1 case of toxic death (gastric hemorrhage) and another with complete duodenal stenosis which required further surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Alpha-2 interferon and 5-fluorouracil in advanced colorectal cancer.

A total of 21 untreated patients (5 males, 16 females; median age, 55 years; range, 28-72) with advanced measurable colorectal carcinoma were treated with an association of 5-fluorouracil (1000 mg/weekly) and alpha-2 interferon (three times a week s.c.: 6 x 10(6) U in the 1st month, 9 x 10(6) U in the 2nd month, 12 x 10(6) U in the 3rd month and then 18 x 10(6) U) until maximum response or progression of disease. Sites of disease involved liver in 10 patients, lung in 6, supraclavicular lymph nodes in 3, skin in 1, abdomen in 4, and vagina in 1 patient. Nine responses (42.8%) were documented (4 complete and 5 partial) with metastases confined to the liver, lung, nodes and skin. Median duration of response was 11 months (range, 4-17+) and median survival was 10 months (range, 2-17+). Side effects (fever, flu-like syndrome and leukopenia) required a dose reduction of 5-fluorouracil in 8 patients and interferon in 2 patients.

Adult↗

PubMed1990

Cisplatin, etoposide, and ifosfamide in non-small cell lung carcinoma. A phase II randomized study with cisplatin and etoposide as the control arm.

A Phase II randomized study testing the combination of cisplatin, etoposide, and ifosfamide (PEI) in non-small cell lung cancer (NSCLC) was performed. The standard combination of cisplatin and etoposide (PE) was used as the control arm. Since January 1987, 78 patients were enrolled and then stratified for previous treatments and performance status (PS). The response rate (RR) of PEI was 26% (95% confidence limits [95 CL], 12% to 40%), with one complete response (CR). The RR of PE was 26% (95 CL, 13% to 39%), with no CR. The median response duration was 5 months (range, 2 to 13 months) for PEI and 4 months (range, 2 to 6 months) for PE. The median survival time was 6 months (range, 1 to 22+ months) for PEI and 7 months (range, 1 to 21+ months) for PE. Leukopenia at recycling was similar in both arms (25% for PEI and 29% of PE). The median leukocyte nadir was 2100/microliters (range, 430 to 4870/microliters) for PEI patients and 3150/microliters (range, 500 to 5000/microliters) for PE patients. Three patients had a drug-related death secondary to infections. This Phase II randomized study suggested that the combination of cisplatin plus etoposide and ifosfamide produces results similar to those obtainable with cisplatin and etoposide.

Adenocarcinoma↗

PubMed1990

Unresectable hepatocellular carcinoma: a prospective controlled trial with tamoxifen.

The liver is an estrogen responsive organ. Clinically, estrogens may play a role in the induction of liver tumors and, experimentally, estrogens are involved in the control of hepatocyte proliferation. The results of a prospective controlled clinical trial using an anti-estrogen, tamoxifen, in patients with unresectable hepatocellular carcinoma (HCC) are presented below. Thirty-eight consecutive cirrhotics with HCC were allocated to either 30 mg/day tamoxifen or no treatment. The two groups of patients were matched for mean age, male/female ratio, Child-Pugh risk group, approximate tumor volume (US and/or CT scan) and etiology of the underlying cirrhosis. The drug appeared to have no side effects. Survival was significantly prolonged in tamoxifen-treated patients with 22% (vs. 5%) survival at 12 months. No differences were observed between males and females or alcoholic and non-alcoholic cirrhosis. In 53% of tamoxifen-treated patients the levels of alpha-fetoprotein dropped and, in this subgroup, survival was further prolonged. Tumor volume, lactate dehydrogenase (LDH) and alkaline phosphatase slowly increased, suggesting a slower, but continuous, progression of the disease. In conclusion, anti-estrogen treatment appears effective in the palliation of unresectable or otherwise untreatable HCC. A reduction in alpha-fetoprotein levels appears to be a favorable prognostic index.

Aged↗

PubMed1990

Modulating fluorouracil with different drugs: the Padua experience.

Several clinical experiences from Padua, Italy confirm that 5-fluorouracil may be usefully modulated by the addition of leucovorin, and especially by platinum and alpha interferon. The intra-arterial and intraperitoneal administration of such synergistic combinations has also proved to be of benefit in special subsets of patients. Perspectives of further studies are examined.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Response and toxicity of cisplatin and 120-h 5-fluorouracil infusion in pretreated and untreated patients with advanced epidermoid cancer of the head and neck.

Eighty-two patients with advanced or recurrent squamous cell carcinoma of the head and neck were treated with bolus cisplatin and 120-h infusion of 5-fluorouracil. Among 49 pretreated patients, there were 9 complete and 12 partial responses, for an overall response rate of 43% and a median estimated survival of 8 months. Hematologic toxicity in this group was relevant, with 4 early deaths and 30% of cases with moderate to severe leukopenia; mucosal and renal toxicities were also important. Among 33 patients with no prior therapy, there were 8 complete and 17 partial responses, for an overall response rate of 76%. Fifteen of the 25 responding patients received subsequent locoregional treatment. The median estimated survival in this group was 29 months. Hematologic, mucosal, and renal toxicities were only mild to moderate. Episodes of possible 5-fluorouracil-related cardiotoxicity were recorded in both pretreated and untreated patients. Twelve of 41 partial responses observed after the second cycle of therapy were converted to complete responses with a third (8 cases) and also a fourth (4 cases) course. This study confirmed that cisplatin plus 5-fluorouracil is a first-choice combination in previously untreated patients. Definitive evidence that chemotherapy can favorable influence survival awaits confirmation by randomized trials, using a control arm with conventional locoregional treatment. In previously treated patients with recurrent disease, less intensive regimens not requiring hospitalization seem more useful for the quality of life.

Adult↗