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F Graziano

Publications and source records attributed to F Graziano.

At least 55 records · Page 3Linked to original sources
PubMed1999

Chemotherapy for advanced pancreatic cancer: it may no longer be ignored.

Two case histories are reported here in which a chemotherapeutic approach improved the clinical conditions of patients with advanced pancreatic cancer. Until recently, chemotherapy was considered ineffective in pancreatic cancer, and most oncologists treated these patients with best-supportive-care only. Enthusiasm for systemic therapy of advanced pancreatic cancer is again growing, spurred by the advent of new drugs and new treatment endpoints such as life quality and symptom palliation. Gemcitabine, the most intensively-investigated new drug in pancreatic cancer, has shown an advantage in both survival and clinical benefit over that of 5-fluorouracil (5-FU). Other new drugs such as taxanes have shown interesting levels of activity, and are deserving of further evaluation. Although these results are far from conclusive and are only partially satisfactory, they represent a significant step forward in the treatment of advanced pancreatic cancer.

Adenocarcinoma↗
PubMed1999

Whole body hyperthermia induction of soluble tumor necrosis factor receptors: implications for rheumatoid diseases.

OBJECTIVE: To test the hypothesis that 41.8 degrees C x 60 min whole body hyperthermia (WBH) induces increased serum levels of soluble necrosis factor receptors (sTNF-R). METHODS: We tested the serum of cancer patients for changes in sTNF-RI and RII levels, as a function of time, pre and post: (1) WBH alone, (2) WBH and chemotherapy, i.e., melphalan (L-PAM), and (3) L-PAM alone. RESULTS: For sTNF-RI there was a marked increase (over pre-treatment values, i.e., 86%) in serum levels after WBH alone (n = 3), which peaked 2.5 h post-WBH; L-PAM (iv) only resulted in a dip in sTNF-RI seen 40 min postadministration; the combination (WBH + L-PAM), resulted in both the dip at 40 min and the increase at 2.5 h post-treatment. For sTNF-RII both WBH alone (n = 3) and WBH + L-PAM (n = 2), there was an increase in receptor serum levels of 25% and 30%, respectively, which peaked 5.5 h post-treatment, and remained elevated at 24 h. L-PAM alone resulted in a dip in levels only at 40 min post-treatment. sTNF-RI and RII levels returned to baseline values within 7 days post-treatment. CONCLUSION: 41.8 degrees C WBH results in transient increases in TNF-RI and RII. These results may have therapeutic implications for the application of WBH to TNF mediated disease processes.

Adult↗
PubMed1998

Expression of p53 protein and resistance to preoperative chemotherapy in locally advanced gastric carcinoma.

BACKGROUND: Inactivation of the p53 gene has been reported to be associated with resistance to chemotherapy. The authors evaluated the significance of p53 status to the clinical outcomes of patients with locally advanced, unresectable gastric carcinoma (LAGC) who received chemotherapy. METHODS: Thirty chemotherapy-naive patients with LAGC received weekly administration of cisplatin 40 mg/m2, epi-doxorubicin 35 mg/m2, 5-fluorouracil 500 mg/m2, 6S-leucovorin 250 mg/m2, and glutathione 1500 mg/m2. After eight administrations of these agents, patients were assessed for response. Biopsy specimens of primary tumors were analyzed for p53 status using monoclonal antibody Bp53-12. RESULTS: Characteristics of patients were as follows: The median age was 66 years (range, 44-70 years); 18 were males and 12 were females. Eastern Cooperative Oncology Group performance status was 0 for 14 patients and 1 for 16. Histology was intestinal for 13 patients; for 17, it was diffuse. The site of the primary tumor was the cardia in 8 patients, the body of the stomach in 13, and the antrum in 9. The response rate (assessed with CT scan and endoscopy) for patients with p53 negative tumors was significantly higher than for those with overexpression of p53 (71% vs. 12%, P=0.004). CONCLUSIONS: p53 status analyzed before chemotherapy seems to be associated with response to treatment in patients with LAGC. This may provide a useful guide to selecting neoadjuvant chemotherapy for these patients.

Adult↗
PubMed1998

S-phase fraction can predict event free survival in patients with pT2-T3N0M0 colorectal carcinoma: implications for adjuvant chemotherapy.

BACKGROUND: Adjuvant chemotherapy for colorectal carcinoma was found to improve survival of patients with American Joint Committee on Cancer/International Union Against Cancer Stage III disease. The usefulness of chemotherapy in patients with Stage II disease continues to be debated, and it is likely that only those patients with a poor prognosis should receive adjuvant chemotherapy. Biologic prognostic factors may allow further insight into the optimal treatment strategy for patients with Stage II or earlier disease. In this study the prognostic role of S-phase fraction (SPF) determined by flow cytometry was assessed in patients with Stage I-II colorectal carcinoma. METHODS: Specimens of surgically resected colorectal carcinoma were examined for SPF by flow cytometric DNA analysis. Consecutive patients referred to the study institution were considered eligible for this study. The main inclusion criteria were a Stage I-II tumor together with sufficient tumor material and adequate follow-up information. For each stage of disease, SPF data were associated with the recurrence rate and the disease free survival (DFS). RESULTS: Analysis was performed on 167 patients (65 with Stage I disease and 102 with Stage II disease). Among Stage I patients, SPF was high in 20 patients and low in 45 patients. In Stage II patients, there were 36 patients with low SPF and 66 patients with high SPF. In both stages, the recurrence rate and DFS were significantly worse for the subgroups of patients with high SPF. CONCLUSIONS: SPF has revealed prognostic differences among patients with surgically resected Stage I-II colorectal carcinoma. These data should be considered for planning future trials in the adjuvant setting because patients with high SPF may benefit from adjuvant chemotherapy.

Adult↗
PubMed1998

Different doses of pamidronate in patients with painful osteolytic bone metastases.

Cancer patients with painful osteolytic bone metastases who had failed initial treatment with hormones and/or chemotherapy were each randomized to receive one of three pamidronate doses as outpatients: 45, 60, 90 mg given every 3 weeks for 12 weeks. Seventy patients were enrolled in this study, for a total of 265 infusions. There were 64 patients who completed 12 weeks of therapy. Forty-eight patients took nonsteroidal antinflammatory drugs, while 22 patients received morphine before pamidronate treatment. A reduction in bone pain and mobility scores was observed in all three different dose groups: in 11 of 23 patients (47%) at 45 mg; in 12 of 24 patients (50%) at 60 mg; and in 16 of 23 patients (69%) at 90 mg. However, while for patients receiving pamidronate at 90 mg median changes in pain and mobility were statistically significant at the 6th week, for patients receiving 45 mg they were not significant until the 12th week and for patients receiving 60 mg, until the 9th week. In weeks 0-6, the daily consumption of analgesics was reduced in 3 patients in the 45-mg arm, in 4 patients in the 60-mg arm, and in 7 patients in the 90-mg arm. In weeks 7-12, the daily consumption of analgesics was reduced in 8 patients receiving 45 mg, in 8 patients receiving 60 mg, and in 7 patients receiving 90 mg. No significant toxicity was recorded. In 2 patients (45 and 90 mg) fever (> 38 degrees C) and myalgia were observed after the first administration. In conclusion, our results seem to confirm the utility of higher doses of pamidronate in patients with painful bone metastases, because of the faster symptom relief achieved.

Adult↗
PubMed1998

Intensive weekly chemotherapy for locally advanced gastric cancer using 5-fluorouracil, cisplatin, epidoxorubicin, 6S-leucovorin, glutathione and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

Local extension prevents curative resection in more than two-thirds of gastric cancer patients. Unfortunately, resectability is one of the main prognostic factors in these patients, and survival is longer when tumours are completely removed. Preoperative chemotherapy is an attractive concept for obtaining curative resection. Thirty-two locally advanced unresectable gastric cancer patients were enrolled in five Italian Group for the Study of Digestive Tract Cancer (GISCAD) centres. For 16 patients, surgical unresectability was based on computerized tomography scan evaluation of tumour size (four patients) and invasion of adjacent structures (12 patients), whereas in another 16 patients locally advanced disease was confirmed by laparotomy. They received weekly administration of cisplatin 40 mg m(-2), 5-fluorouracil 500 mg m(-2), epidoxorubicin 35 mg m(-2), 6S-stereoisomer of leucovorin 250 mg m(-2) and glutathione 1.5 g m(-2). From the day after to the day before each chemotherapy administration, filgrastim was administered by subcutaneous injection at a dose of 5 microg kg(-1). One cycle of therapy consisted of eight weekly treatments. Fifteen of 32 patients (47%) responded to chemotherapy, whereas 13 (41 %) had stable disease and four (12%) progressed on therapy. Of the 15 responding patients, 13 were completely resected after chemotherapy and two of them had a complete pathological response. Two clinically responding patients were found unresectable at operation because of peritoneal seeding. At a median follow-up from the start of treatment of 24 months (range 11-39 months), 10 of 13 resected patients are alive and eight are relapse free. Three patients died after 11, 12, and 14 months respectively. Toxicity was acceptable: side-effects consisted mainly of grade II National Cancer Institute common toxicity criteria (NCICTC) leucopenia and thrombocytopenia in ten patients. Neither treatment-related death nor surgical complications in patients undergoing surgery were observed. This weekly intensive regimen enabled resection in half of previously inoperable tumours with a moderate toxicity. It can be offered to patients with locally advanced unresectable gastric cancer to obtain curative resection.

Adult↗
PubMed1998

Phase II study of paclitaxel in pretreated advanced gastric cancer.

Patients with advanced gastric cancer unresponsive or progressing after PELF chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six patients entered the study, and all of them were evaluable for response and toxicity. Toxicity was mild: apart from alopecia, grade 3 toxicities were leukopenia and thrombocytopenia in six patients, and grade 2 neurotoxicity in seven patients. Eight patients (22.2%, 95% CI: 9-35%) achieved an objective response, with a median duration of 5 months. Median survival time for all patients was 8 months. In 16 of 36 patients (44%), treatment determined a significant relief of symptoms. Out-patient paclitaxel given over 3 h may be effective as salvage treatment in patients with advanced gastric cancer refractory to first line chemotherapy.

Adult↗
PubMed1998

[Surgical resection of lung metastases from breast cancer. Report of 12 cases].

Thirty-nine patients affected with lung metastases from different primary neoplastic sites have been treated between 1990 and 1998 at 2nd Surgical Division of "Regina Elena" National Cancer Institute of Rome. Among them, 12 were metastases from breast cancer-lung metastases were isolated in 9 cases and multifocal in 3 cases, although always in the same lung. Nine cases underwent a thoracotomic approach: in 6 patients we have performed a wedge resection, in 3 cases a lobectomy. Three patients underwent a wedge resection by means of a video-thoracoscopic approach. We have registered 2 post-operative complications and no deaths. Median survival rate was 40 months and 5 year actuarial survival rate was 42%. Surgery for isolated lung metastases seen to be a safe approach and to improve life expectancy in most of patients.

Adult↗
PubMed1997

A randomized, controlled phase III study of cyclophosphamide, doxorubicin, and vincristine with etoposide (CAV-E) or teniposide (CAV-T), followed by recombinant interferon-alpha maintenance therapy or observation, in small cell lung carcinoma patients with complete responses.

BACKGROUND: Studies of chemotherapy for patients with small cell lung carcinoma (SCLC) have shown that teniposide (T) may have higher activity than etoposide (E). In this randomized, controlled Phase III study, the authors compared cyclophosphamide, doxorubicin, and vincristine (CAV) with E and CAV with T as induction treatments for patients with SCLC. A second objective of the study was to study patients who had achieved complete response (CR). They were considered for a second randomization to maintenance therapy, in which they would receive either recombinant interferon-alpha (rIFN-alpha) or no treatment. METHODS: From June 1990 to December 1995, 140 untreated SCLC patients were enrolled in this study. Patients were stratified by either limited disease (LD) or extensive disease (ED) and randomized to one of two treatment arms. The schedules for both arms included cyclophosphamide 1000 mg/m2 administered intravenously (i.v.), doxorubicin 50 mg/m2 i.v., and vincristine 2 mg i.v. on Day 1. Arm A (CAV-E) involved the addition of E 100 mg/m2 i.v. on Days 2, 3, and 4; Arm B (CAV-T) involved the addition of T 60 mg/m2 i.v. on Days 2, 3, and 4. Courses were repeated every 3 weeks. After 3 courses, patients with LD received chest radiotherapy and 2 additional consolidation courses, whereas patients with ED received 5 consecutive courses only. Patients with CR were considered for the second randomization, which consisted of either maintenance therapy with intramuscular (i.m.) rIFN-alpha-2b, 3 M.U., once a day for 9 months (IFN-alpha arm) or no therapy (control arm). RESULTS: At 5 years from start-up (3-year median observation time and 90% death rate), the study was closed. Results were as follows: 140 patients (71 in Arm A and 69 in Arm B) were eligible for survival analysis; 131 were evaluable for response and toxicity (66 in Arm A and 65 in Arm B), whereas 9 were not (6 early deaths and 3 with protocol violations). Among evaluable patients, 68 showed LD (35 assigned to Arm A and 33 to Arm B); the responses to treatment were 28.5% (10/35) CR and 51% (18/35) partial response (PR) to CAV-E, and 39% (13/33) CR and 39% PR (13/33) to CAV-T. Sixty-three patients showed ED (31 assigned to Arm A and 32 to Arm B); their responses were 22.5% (7/31) CR and 52% (16/31) PR to CAV-E, and 12.5% (4/32) CR and 50% (16/32) PR to CAV-T. Drug-related toxicity was WHO Grade 3-4 myelosuppression in 20% of 292 CAV-E courses and in 27% of 252 CAV-T courses. There were 6 toxic deaths, 1 in Arm A and 5 in Arm B (chi-square = 2.86); 2 patients in Arm A discontinued therapy due to persistent leukopenia and thrombocytopenia. No other remarkable toxicities were observed. Actuarial median survival (MS) was 13.7 months (range, 1.0-62.5 months) for patients with LD receiving CAV-E (Arm A) and 15.2 months (range, 0.5-68.2 months) for those receiving CAV-T (Arm B) (chi-square = 0.89); in patients with ED it was 10.5 months (range, 0.6-30.4 months) and 8.2 months (range, 0.2-24.8 months), respectively (chi-square = 3.42). Overall, MS was 12 months (range, 0.6-62.5 months) in Arm A and 10 months (range, 0.2-68.2 months) in Arm B (chi-square = 0.059). Thirty-nine patients with CR (27.8%) were candidates for the second randomization. Among them, 26 patients (18.5%) complied with the program and were randomized as follows: 14 were assigned to the IFN-alpha arm and 12 to the control arm. Starting from the second randomization, median time to progression was 12 months (range, 3-51 months) for patients in the IFN-alpha arm versus 7 months (range, 1-59 months) for patients in the control arm (chi-square = 0.12). MS was 15 months (range, 5-52.3 months) versus 9 months (range, 2-60.5 months) (chi-square = 0.13). CONCLUSIONS: This study did not show a wide difference in activity and toxicity between CAV-E and CAV-T. The number of patients who entered the second randomization was too small to reach the second study endpoint.

Adult↗
PubMed1997

A phase I study of paclitaxel and 5-fluorouracil in advanced gastric cancer.

This is a phase I study to determine the maximum tolerated dose (MTD) and toxicity of a combination of paclitaxel and 5-Fluorouracil (5-FU) in advanced gastric cancer patients. The patients, refractory to the PELF regimen (5-FU, leucovorin, cisplatin, epidoxorubicin), received weekly 5-FU at the fixed dose of 500 mg/m2, and escalating doses of paclitaxel every 3 weeks with a starting dose of 150 mg/m2 given as in 3-h infusion. The dose was escalated by 25 mg/m2 every 3 patients. Fifteen patients entered the study. The upper paclitaxel dose (225 mg/m2) was given to 6 patients. Up to this dose, no severe toxicity (grade 3-4) was recorded. Apart from alopecia, grade 1-2 leukopenia occurred in 5 patients and grade 1-2 neurotoxicity in 2 patients. All patients were evaluable for response (at least 2 cycles): 2 patients achieved an objective response (200 and 225 mg/m2). In 6 patients, treatment resulted in notable relief from symptoms. Out-patient paclitaxel given over 3 h and 5-FU may be combined safely for the treatment of patients with advanced gastric cancer. The recommended doses for phase II study are paclitaxel 225 mg/m2 and 5-FU 500 mg/m2.

Adult↗
PubMed1997

The clinical impact of teniposide in the treatment of elderly patients with small-cell lung cancer.

Teniposide (VM26) has been claimed to be active with a moderate toxicity in elderly patients affected by small-cell lung cancer (SCLC). Twenty-two patients with SCLC older than 65 years received VM26 as first-line chemotherapy at a dose of 60 mg/m2 on 5 consecutive days every 3 weeks. Age distribution ranged from 67 to 80 years (median 72 years). Fourteen patients were men and eight were women. Twelve patients had limited disease (LD) and ten extensive disease (ED). One patient (LD) had a complete response, and four (3 LD, 1 ED) achieved a partial response for an overall response rate of 22.7% (95% CI 6-40%). The most frequent toxicity was myelosuppression: 20 and 15% of patients had grade 3 leukopenia and thrombocytopenia, respectively. Our results seem to suggest that VM26 by this schedule is moderately effective in elderly patients with SCLC, and it cannot be recommended as a routine treatment.

Aged↗
PubMed1996

Consolidation biochemotherapy for patients with advanced nonsmall cell lung carcinoma responding to induction PVM (cisplatin, vinblastine, mitomycin-C) regimen. A phase II study.

BACKGROUND: The authors investigated a consolidation biochemotherapy program with subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN alpha) biologic response modifiers (BRM) in patients with advanced nonsmall cell lung carcinoma (NSCLC) with responsive or stable disease to induction chemotherapy. METHODS: Patients with proven, advanced, previously untreated NSCLC were entered into the study. Induction chemotherapy consisted of cisplatin, 120 mg/m2 intravenously (i.v.), on Day 1; vinblastine, 6 mg/m2 i.v., on Day 1; and mitomycin-C, 6 mg/m2 i.v., on Day 1 (PVM), every 3 weeks. Subsequently, patients with complete response (CR), partial response (PR), and stable disease (SD) received consolidation biochemotherapy with subcutaneous rIL-2, 3 MU/m2 twice/day, and rIFN alpha, 3 MU once/day, 5 days a week, starting 2 weeks after the second PVM course. After 3 and 6 weeks of BRM treatment, patients had a 14-day rest period to intercalate consolidating PVM courses. RESULTS: Seventy-seven patients were enrolled in the trial. After 2 PVM induction courses, 16 patients progressed and went off the study, whereas 61 patients were eligible for consolidation biochemotherapy. Among the 61 patients, 9 were not treated with BRM for several reasons, whereas 52 patients began biochemotherapy and were evaluable for toxicity. Furthermore, a few days after starting BRM, 9 patients discontinued therapy due to side effects; the remaining 43 patients received adequate treatment and were fully evaluable. In the 52 evaluable patients, the following BRM related toxicities were observed: World Health Organization (WHO) grade 2-3 fever in 85% of patients, asthenia in 71%, anorexia in 63%, and flu-like syndrome in 18.5%. PVM-related vomiting was present in 19% of patients. WHO Grade 3-4 myelosuppression, from both BRM and PVM (overlapping toxicity), was anemia in 16% of patients, leukopenia in 12%, and thrombocytopenia in 19%. There were three toxic deaths: two due to BRM-induced hypotension and one from pneumonia. In the 43 fully evaluable patients (23 PR and 20 SD after induction chemotherapy), after a median of 6 weeks of biochemotherapy (range, 3-16 weeks), we observed 5 of 20 patients achieving PR from SD, and 6 of 23 with confirmed PR. In these 11 patients, the median duration of response was 21 weeks (range, 7-80 weeks). Overall response improvement was 11.6% in the 43 patients and 6.4% in the 77 total enrolled patients. Median survival was 41 weeks (range, 15-173 weeks) in the 43 patients and 38 weeks (range, 1.4-173 weeks) in the 77 patients. CONCLUSIONS: In this study, biochemotherapy, when administered by this dose and schedule, did not offer substantial benefit although it caused significant toxicity.

Adult↗
PubMed1995

Symptomatic, stage IV, non-small-cell lung cancer (NSCLC): response, toxicity, performance status change and symptom relief in patients treated with cisplatin, vinblastine and mitomycin-C.

In a series of 46 symptomatic patients with metastatic, stage IV, non-small-cell lung cancer (NSCLC), we used a three-drug combination with cisplatin (120 mg/m2), vinblastine (6 mg/m2) and mitomycin-C (6 mg/m2) (PVM), repeated every 3 weeks. After two courses, we observed that none of the patients had achieved a complete response; 33% (15/46) had partial response (95% confidence limits: 19.2-46.8); 39% (18/46), stable disease and 28% (13/46), progressive disease. Median response duration was 14.0 weeks (range, 4-36.7), median time to progression 22.4 weeks (range, 7-44.4), and median survival time 26.4 weeks (range, 1-103). WHO grade III-IV myelotoxicity occurred in 15.2% of the courses administered, affecting 39.5% of patients, and severe nephrotoxicity was observed in 9.3% of patients. No toxic death occurred. The post-treatment KPS score increased in 7 patients with partial response (47%), 4 with stable disease (22%) and 1 with progressive disease (8%), while it decreased in 3 patients with partial response (20%), 3 with stable disease (17%) and 10 with progressive disease (77%). In all, KPS increased in 12/46 cases (26%). However, no statistically significant difference was observed when the KPS score before and after treatment was compared in the total group of patients or when it was compared in the total group of patients or when it was compared in responders and in non-responders. After chemotherapy, there was complete disappearance of at least one symptom in 27.1% of cases and improvement in 27.1%. Overall, major symptom control occurred in 54.3% of cases, with a median palliation time lasting 10 weeks (range, 4-32). Patients with partial remission and stable disease achieved symptomatic palliation in 90% and 55.5% of cases, respectively. When we compared the palliation rate between responders and non-responders, a significant difference was noted (Chi-square test: P < 0.05). Although our schedule did not produce a higher objective response rate and the KPS score was not significantly improved, the symptom palliation appeared worthwhile considering the highly unfavourable prognosis of the patients investigated.

Adult↗
PubMed1995

Continuing medical education through the videotex system in Italy.

Continuing education for medical doctors is not compulsory in Italy. The link with the university is lost shortly after the final medical examination, and there is no other teaching institution for structured continuing medical education (CME). Distance learning gives physicians the opportunity to use updating programs at home at their convenience. Videotel, the Italian videotex system, is the first telematic tool that, at low cost, can reach every home nationwide. Through this system information can be exchanged 24 hours a day, using the Videotel database as central memory, the telephone network as connecting system, and low-cost devices as peripherals. The authors evaluated the technical capacity and didactic efficacy of the Videotel system as a vehicle for CME (in both oncology and general medicine). In an exploratory phase they surveyed physicians of the Italian Province designated for the study, with the objective of promoting the initiative and enrolling physicians interested in this innovative approach to CME. Teachers at Italian universities provided the educational material: interactive lessons, clinical case discussions and problem solving, and multiple-choice questions. Twenty-nine physicians agreed to participate. Despite the interest shown by these physicians, they made very little use of the didactic database. The main reasons for failure to connect with the educational database were the lack of time and unfamiliarity with the instrument. Although the results of the study were discouraging, the authors believe that the resolution of technical problems linked with the system and an increasing familiarity of physicians with telematic and informatic tools in general, together with appropriate incentives, will make the videotex system a feasible, low-cost, efficient vehicle for CME.

Adult↗
PubMed1995

Synchronous primary hepatic lymphoma and epidermoid lung carcinoma treated with chemotherapy and surgery.

While involvement of the liver by non-Hodgkin's lymphoma is a relatively frequent event, primary liver lymphoma is an uncommon disease. We describe a case of synchronous primary hepatic lymphoma and epidermoid lung carcinoma occurring in a 61-year-old male patient. Complete remission of both diseases was achieved with a radical approach, which included combination chemotherapy and surgery. The patient has now been in persisting complete remission for 40 months after surgery.

Antineoplastic Combined Chemotherapy Protocols↗