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Biomedical subjects

A De Paoli

Publications and source records attributed to A De Paoli.

At least 19 recordsLinked to original sources
PubMed2005

Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study.

BACKGROUND: The aim of the study was to evaluate tolerance and efficacy of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally advanced, resectable, rectal cancer. PATIENTS AND METHODS: Fifty-three patients with potentially resectable T3, N0-2 (87%) and T4, N0-2 (13%) rectal cancer were treated with capecitabine (825 mg/m2, twice daily for 7 days/week) and concomitant RT (50.4 Gy/28 fractions). Patients underwent surgery after 6-8 weeks followed, upon physician's indications, by 4-months adjuvant capecitabine. The primary end point was to determine the rate of pathologic complete response. Secondary end points were to assess the rate of clinical response and the safety profile. RESULTS: All patients but two completed the RT programme and 47 (89%) received 81%-100% of the capecitabine dose (100% of dose in 72% patients, 81%-95% in 17% patients and 48%-74% in 11% of patients). No patient had grade 4 toxicity. Grade 3 toxicity occurred in six patients (11%) and consisted mainly of leucopenia (4%) and hand-foot syndrome (4%). Mild or moderate toxicity was common and included leucopenia (72%), diarrhea (40%), proctitis (34%) and skin toxicity (20%). The overall clinical response rate was 58% and the downstaging rate was 57%, with a pathologic complete response rate of 24%. Among 34 patients with low-lying tumors (<or=5 cm from anal verge), 20 (59%) had a sphincter-saving operation. CONCLUSIONS: Preoperative chemoradiation with capecitabine and RT appeared to be effective in locally advanced resectable, rectal cancer. The favorable safety profile of the combination might warrant the use of capecitabine and RT with other effective new drugs.

Administration, Oral↗
PubMed2005

Nasal continuous positive airway pressure: does bubbling improve gas exchange?

In a randomised crossover trial, 26 babies, treated with Hudson prong continuous positive airway pressure (CPAP) from a bubbling bottle, received vigorous, high amplitude, or slow bubbling for 30 minutes. Pulse oximetry, transcutaneous carbon dioxide, and respiratory rate were recorded. The bubbling rates had no effect on carbon dioxide, oxygenation, or respiratory rate.

Carbon Dioxide↗
PubMed2003

Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomised protocol.

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive previously untreated patients with MM received chemotherapy within the prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were evaluable for both response and long-term survival and 244 (94.6%) have died. The median survival of all patients was 40 months (6-162 months). The median survival did not differ between patients who had complete response (CR) (50 months (9-162 months)), partial response (PR) (46 months (8-147 months)) or stable disease (SD) (41 months (7-135 months)). The median survival was shorter (13.6 months (6-135 months)) (P<0.0001) in patients whose disease progressed while they were receiving first induction chemotherapy. Causes of death were more frequently (P=0.04) related to MM in patients who had progressive disease (PD) than in patients who had a CR or PR or SD. The main clinical and laboratory characteristics were similar in the four groups. These data indicate that patients who maintain SD during first-line chemotherapy have a prognosis similar to that of patients who attain a response. Only patients whose disease progresses have a distinctly worse outcome.

Analysis of Variance↗
PubMed2003

Ifosfamide in the adjuvant therapy of soft tissue sarcomas.

Ifosfamide and anthracyclines are the only active agents in advanced soft tissue sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was reintroduced in the clinic after the discovery of mesna which prevents its typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting, doxorubicin was used alone or in combination in the first-generation trials, whereas its parent compounds epirubicin and ifosfamide were employed in the second-generation adjuvant trials, which started in the early 90s. Other relevant aspects of the second-generation trials are the use of the hematopoietic growth factors and the increase of the dose intensity, the introduction of more restrictive selection criteria and the use of the two most active agents, ifosfamide and anthracyclines. Only the Italian cooperative trial has been concluded, and the results reported and updated. After a median follow-up of 89.6 months (range 56-119), the intention-to-treat analysis still reveals a difference in overall survival which, however, is not statistically significant. However, the 5-year overall survival estimate, which is a reasonable end point for the survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and 46.1% for the treatment and the control groups, respectively (p = 0.04).

Antineoplastic Agents, Alkylating↗
PubMed2003

Intraoperative radiation therapy for retroperitoneal soft tissue sarcomas.

Treatment of retroperitoneal soft tissue sarcomas is a difficult clinical problem. Despite the improvement in resection rates in the most recent surgical series, local control still remains the main problem because of the high incidence of local recurrences after surgery. Postoperative radiation therapy has not been always successful because of dose-tolerance of surrounding normal structures, which prevent the delivery of adequate doses of radiation. To overcome this limitations, new therapeutic approaches including external-beam radiation and intraoperative radiation therapy (IORT) have been evaluated at some Institutions. The results of IORT with or without external-beam radiation are reviewed and our experience with preoperative radiation and IORT is reported. As treatment of retroperitoneal sarcomas has evolved into combined modalities including preoperative radiation, maximum surgical resection and IORT, a possible improvement in local control rates has been achieved. However, locoregional failures and the incidence of distant metastases remain a challenge, emphasising the need for further improvement in local and distant treatment. The new phase II trial, activated within the Italian Sarcoma Group, with preoperative concurrent chemo-radiation therapy and IORT is presented.

Combined Modality Therapy↗
PubMed2002

Prognostic factors in soft tissue sarcomas: a study of 395 patients.

AIMS: The aim of this study was to report prognostic factors, end-points of local recurrence, distant recurrence, post-metastasis survival, and overall survival in a cohort of patients with soft tissue sarcomas. METHODS: We analysed a database of 395 patients affected by primary soft tissue sarcomas of various primary sites, treated and followed up at the Centro di Riferimento Oncologico, Aviano, Italy from January 1985 to January 1997. RESULTS: Grade, size, stage, surgical margins, distant metastasis, age, sex, performance status, and haemoglobin value were significant for overall survival. Histology, grade, stage, and surgical margins were significant for local recurrence. Grade, size, and stage, were significant for distant recurrence; and surgical margin was significant variable for post-metastasis survival. CONCLUSIONS: Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic significance for overall survival and distant recurrence than for local relapse. Positive surgical margins are the main predictors for local relapse. Age was the most consistent adverse independent prognostic factor for survival.

Adolescent↗
PubMed2001

Radiotherapy and continuous infusion 5-fluorouracil in patients with nonresectable pancreatic carcinoma.

PURPOSE: The current standard local treatment for nonresectable pancreatic carcinoma is radiotherapy (RT) with concurrent 5-fluorouracil (5-FU); however, the optimal schedule for 5-FU administration has not been fully established. In this study, we report on our experience with the combination of RT and continuous infusion 5-FU in a group of patients with locally nonresectable pancreatic carcinoma. METHODS AND MATERIALS: Forty-two patients with adenocarcinoma of the pancreas were enrolled in a prospective clinical trial. RT was delivered using a four-field technique to a total dose of 59.4 Gy in 33 fractions. 5-FU was given through a central venous catheter at a dose of 300 mg/m(2)/day, 7 d/wk, throughout the entire course of RT. RESULTS: All patients completed the RT as planned, and 33 (78%) completed the full regimen of chemotherapy. Ten patients (23%) had a partial response, and 32 (77%) had stable disease. Subjective response, defined as the disappearance of symptoms observed at diagnosis, was also evaluated. Two patients (6%) had a complete, and 24 (75%) a partial, remission of symptoms. The median time to progression was 6.2 months, and the median survival time was 9.1 months. CONCLUSIONS: In terms of local control, the results of our study, with RT and protracted 5-FU infusion, compare well with those of other studies using RT and bolus 5-FU. The control of distant metastatic disease remains an open issue. However, the palliation of symptoms achieved by our treatment schedule in patients with a very poor prognosis and severe symptoms may be regarded as a positive result.

Adenocarcinoma↗
PubMed2001

Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: results of the Italian randomized cooperative trial.

PURPOSE: Adjuvant chemotherapy for soft tissue sarcoma is controversial because previous trials reported conflicting results. The present study was designed with restricted selection criteria and high dose-intensities of the two most active chemotherapeutic agents. PATIENTS AND METHODS: Patients between 18 and 65 years of age with grade 3 to 4 spindle-cell sarcomas (primary diameter > or = 5 cm or any size recurrent tumor) in extremities or girdles were eligible. Stratification was by primary versus recurrent tumors and by tumor diameter greater than or equal to 10 cm versus less than 10 cm. One hundred four patients were randomized, 51 to the control group and 53 to the treatment group (five cycles of 4'-epidoxorubicin 60 mg/m(2) days 1 and 2 and ifosfamide 1.8 g/m(2) days 1 through 5, with hydration, mesna, and granulocyte colony-stimulating factor). RESULTS: After a median follow-up of 59 months, 60 patients had relapsed and 48 died (28 and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The median disease-free survival (DFS) was 48 months in the treatment group and 16 months in the control group (P =.04); and the median overall survival (OS) was 75 months for treated and 46 months for untreated patients (P =.03). For OS, the absolute benefit deriving from chemotherapy was 13% at 2 years and increased to 19% at 4 years (P =.04). CONCLUSION: Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an intensified treatment in similar cases. Although cure is still difficult to achieve, a significant delay in death is worthwhile, also considering the short duration of treatment and the absence of toxic deaths.

Adolescent↗
PubMed2000

Hepatic amyloidosis with light chain deposition disease. A rare association.

Monoclonal immunoglobulin deposition diseases are due to pathological protein deposition in various tissues and organs. Protein deposits may be found in a single tissue or systemically and the organs most frequently involved are kidney, heart, peripheral nerves and the liver. Depending on the pattern of the deposits and the type of immunoglobulin, these diseases are distinguished as primary amyloidosis, light chain deposition disease. Differential diagnosis is made in tissue specimens: microscopically by the identification of positive Congo red staining of the deposits, by immunohistochemical demonstration of proteins reacting with light chain (lambda or kappa) antisera or by recognition of fibrillar structures on electron microscopy. We report an unusual case of light chain deposition disease associated with amyloidosis, where hepatomegaly was the presenting manifestation and liver failure the cause of death, without any kidney involvement.

Amyloidosis↗
PubMed2000

Fludarabine and cladribine in relapsed/refractory low-grade non-Hodgkin's lymphoma: a phase II randomized study.

BACKGROUND: It is unclear whether the purine analogs fludarabine (Flu) and cladribine (CdA) are non-resistant. PATIENTS AND METHODS: Sixty patients with relapsed or refractory low-grade NHL were randomly allocated to initial treatment with either Flu 25 mg/m2, or CdA 0.14 mg/kg, each for five consecutive days every four weeks. Upon treatment failure, eligible patients were crossed over to the other study drug. RESULTS: Overall response and CR were 68% and 48% with Flu, and 72% and 38% with CdA, respectively. For responders, actuarial three-year progression-free survival was 58% with Flu and 52% with CdA. Treatment with both drugs was well tolerated, with toxic effects primarily hematological. Two patients (8%) in the Flu group and 15 patients (47%, P = 0.001) in the CdA group were taken off study because of persistent hematological toxicity. After cross over, none of seven refractory patients responded, while eight of nine previously responsive patients achieved second responses. CONCLUSIONS: Our study confirms that Flu and CdA have similar response rates and durations. However, further studies are required to optimize the CdA schedule and dosage in order to ameliorate its toxic profile while maintaining antitumor activity. The two drugs appear to be cross-resistant.

Adult↗
PubMed2000

Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma.

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57-2.42; P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months; P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients.

Adult↗
PubMed1998

Relevance of age on survival of 341 patients with multiple myeloma treated with conventional chemotherapy: updated results of the MM87 prospective randomized protocol. Cooperative Group of Study and Treatment of Multiple Myeloma.

Age could influence the prognosis of multiple myeloma patients treated with conventional chemotherapy. Between January 1987 and March 1990, 341 consecutive previously untreated patients with multiple myeloma received chemotherapy within the prospective, multicentre, randomized Protocol MM87. Survival was evaluated in patients aged > or < or = 66 years (the median age for the whole series) and in a subgroup of patients aged < 55 years. These groups were similar for main clinical characteristics, including results of cytostatic treatment. As of May 1996, 271 (79%) of the 341 patients had died, and median follow-up of the 70 (21%) living patients was 82 months. Overall, younger patients survived longer than older ones. In fact, in patients > and < or = 66 years, median survival was 31 and 44 months (P < 0.00095) and the percentage of patients surviving over 72 months was 17% and 32% (P = 0.0018) respectively; in patients < 55 years, these figures were 57 months and 35% respectively (P = 0.02 and 0.01, with respect to patients aged > 55 years). In all groups, about 50% of the patients surviving over 72 months had stage I disease. For multiple myeloma patients treated with chemotherapy, survival is favourably affected by relatively young age and early stage of disease.

Adult↗
PubMed1997

Increasing 4'-epidoxorubicin and fixed ifosfamide doses plus granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: a pilot study.

PURPOSE: To determine the maximum-tolerated dose (MTD) of 4'-epidoxorubicin (EPI) in combination with full dose of ifosfamide (IFO) when granulocyte-macrophage colony-stimulating factor (GM-CSF) was used, to estimate its clinical efficacy, and to evaluate the mobilization of hematopoietic progenitors. PATIENTS AND METHODS: Previously untreated advanced patients were treated with fixed doses of IFO at 1.8 g/m2/d for 5 days and escalating doses of EPI. The starting dose level of EPI was 50 mg/m2 bolus on days 1 and 2; subsequent levels were 60 mg/m2 and 70 mg/ m2 given on days 1 and 2. GM-CSF (5 micrograms/kg/d) was administered from days +6 to +19. Clinical evaluation of response was performed after three consecutive cycles. Mobilization of hematopoietic progenitors was evaluated as day 14 CFU-GM after the first cycle only. RESULTS: Overall, six, 18, and 13 assessable patients were entered onto each EPI dose level, respectively. The first and the second EPI level were considered feasible. Conversely, at the third level, only six of 13 patients [46%] tolerated full EPI doses at the scheduled time. Therefore, the dose-intensity of the three levels was 100%, 99.7%, and 86.1%, respectively. Overall, 20 of 37 patients (54%) obtained an objective response. The response rates for the three EPI dose levels were significantly different [17%, 33%, and 100%, respectively; test for trend, P < .001]. Considering only lung metastases, the overall response rate was 72% (20%, 66%, and 100% for the three EPI levels, respectively). The most relevant mobilization effect was obtained at the third EPI level, when both GM-CSF and IL-3 were used as in vitro-stimulating factors. CONCLUSION: The third EPI level (70 mg/m2 on days 1 and 2) is the MTD of this program, since it was administered, without dose reduction or treatment delay, for three consecutive cycles in less than half of the patients. Nevertheless, this level proved to be interesting with regard to response rate (13 of 13 objective responses) and in mobilization of the hematopoietic progenitors.

Adult↗
PubMed1996

Experience with poorly myelosuppressive chemotherapy schedules for advanced myeloma. The Cooperative Group of Study and Treatment of Multiple Myeloma.

In a multicentre study, 83 patients with advanced and previously uniformly treated multiple myeloma (MM) were randomised between cyclophosphamide (600 mg m-2) and epirubicin (70 mg m-2), administered every 3 weeks for three courses and both associated with prednisone and interferon-alpha2b. Both regimens were administered on an outpatient basis and had low haematological toxicity. Clinical results were similar. Overall response rate (43%) and median response and survival (5.9 and 14.1 months respectively) compare well with those obtained with more aggressive chemotherapy schedules.

Adult↗
PubMed1995

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers. A single-institution study.

BACKGROUND: Patients with advanced, inoperable head and neck cancers have cure rates of approximately 10-15%. In these patients, concomitant chemoradiotherapy seems to improve local control and survival. 5-Fluorouracil (5-FU) administered by continuous infusion and cisplatin plus concomitant conventional radiation therapy may be promising in treating advanced, inoperable head and neck cancers. METHODS: Forty-five evaluable patients with primary nonmetastatic, inoperable head and neck cancers were treated. From January 1987 to April 1988, the patients were treated with cisplatin plus radiation therapy (Group 1) and from May 1988 to November 1990, they were treated with the same combination plus 5-FU, given in continuous infusion (Group 2). Clinical and pathologic responses were assessed after radiation therapy was completed. Patients who relapsed underwent salvage surgery, if possible. The disease free and overall survival rates of the patients were evaluated. RESULTS: The overall response rate (complete and partial response) was 93%, 60% of which comprised complete remissions. Despite the high response rates obtained in the two groups, the time to progression for complete responses and the median survival time were unsatisfactory (13 [Group 1] and 10 months [Group 2] and 17 [Group 1] and 16 months [Group 2], respectively). The toxicity rate from the two treatments was not relevant. A Grade II mucositis, according to the World Health Organization, was found in 25 patients, and the treatment was interrupted for 7-10 days in 5. CONCLUSIONS: In this study, despite an improvement in the number of complete responses, the chemotherapeutic regimen with or without 5-FU did not prolong the overall patient survival significantly.

Adult↗
PubMed1994

Total body irradiation and prednimustine in chronic lymphocytic leukemia and low grade non-Hodgkin's lymphomas. A 9-year experience at a single institution.

BACKGROUND: The efficacy and toxicity of total body irradiation (TBI) in patients with chronic lymphocytic leukemia (CLL) and low grade non-Hodgkin's lymphomas (NHL) were evaluated. METHODS: Between January 1984 and September 1992, 81 consecutive patients, 40 affected with CLL and 41 with low grade NHL, with symptomatic Stage III and IV disease, were treated with TBI followed by prednimustine. TBI was given with a 6 MV linear accelerator, applying two opposite alternating fields, including total body, with two fractions of 15 cGy given per week (3-day interval). A total dose of 150 cGy was given over 5 weeks. Six to nine courses of prednimustine (100 mg/m2 orally for 5 consecutive days every 4 weeks) was administered 2 months after TBI treatment as consolidation therapy. RESULTS: Of 40 patients with CLL, 18 (Group I; median age 58.5 years) were younger than 65 years and 22 (Group II; median age 73 years) were older. The overall response rates were 78% in Group I and 91% in Group II, with a median response time of 16.5 and 16 months, respectively. Hematologic toxicity was 72% in Group I and 73% in Group II. It was reversible in all but one heavily pretreated patient who died of progressive anemia and thrombocytopenia after TBI alone. In the 40 patients with CLL, the response rate was 85%; there were 5 complete responses (CRs) (12.5%) and 29 partial responses (PRs) (72.5%). Of the 41 patients with NHL, 29 (Group I; median age 55 years) were younger than 65 years and 12 (Group II; median age 71.5) were older. The overall response rate in both groups was 83%, with median response times of 18.5+ and 14.5+ months for Groups I and II, respectively. Hematologic toxicity was 59% in Group I, whereas it was 50% in Group II. It was reversible in all patients. Overall, in the 41 patients with symptomatic Stage III and IV low grade NHL, the response rate was 82.8%; there were 10 CRs (24.3%) and 24 PRs (58.5%). The prednimustine regimen was generally well tolerated. CONCLUSIONS: In our experience, TBI given in a dose of 150 cGy in 10 fractions twice a week, followed by prednimustine, is an effective treatment for patients with CLL and patients with low grade NHL. This treatment also is effective in patients older than 65 years. The toxicity is acceptable, particularly when TBI and prednimustine are given as initial treatment. Pretreated patients should be monitored strictly.

Age Factors↗
PubMed1994

Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cystostatic policy. Cooperative Group of Study and Treatment of Multiple Myeloma.

The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy. Patients with untreated stage I MM (defined according to Durie and Salmon) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone (MP-P) just after diagnosis; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until relapse. With resistant, progressive or relapsing disease, patients originally treated with MPH-P for induction received combination chemotherapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Combination chemotherapy was more myelotoxic than MPH-P and, in particular, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter the median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 months in stage II and was 24.3 months in stage III patients, still independent of both induction and post-induction policies. In MM, the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved. Both MPH-P and and the association of PTC, VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen, but PTC-VCR-P causes more side effects. Thus, the overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early diseases.

Antineoplastic Agents↗