Biomedical subjects

A Paccagnella

Publications and source records attributed to A Paccagnella.

At least 19 recordsLinked to original sources

PubMed1998

Long term results of surgery and chemotherapy in small cell lung cancer.

OBJECTIVE: The aim of the study is to analyse long-term results of patients with small cell lung cancer (SCLC) treated at the same institution according to a prospective study including surgery, chemotherapy, and radiotherapy. METHODS: From 1981 to 1995, 104 patients with a proven histology of SCLC underwent surgery, chemotherapy, and radiotherapy. Fifty-one patients with operable stage I or II lesion received surgical resection followed by adjuvant chemotherapy and radiotherapy. Fifty-three patients with proved SCLC and clinical stage III received induction chemotherapy followed by surgery and radiotherapy. All patients received from four to six courses of chemotherapy and 36 had prophylactic cranial irradiation (PCI). All patients had follow-up for at least 1 year, and survival time was calculated from the date of the diagnosis until death or most recent follow-up. RESULTS: Ninety-six patients were male and eight female. We performed 29 pneumonectomies, eight bilobectomies, 66 lobectomies and one no resection. Regarding the clinical stage, 35 patients (33.6%) had stage I, 16 patients (15.4%) had stage II and 53 (51%) had stage III. Post-operative pathologic staging revealed stage I in 37 patients (35.6%), stage II in nine patients (8.6%), stage III in 45 patients (43.3%), and in 13 patients (12.5%) there was no more tumor. The 30-day mortality was 2% (two patients). Fourteen patients (13.4%) had post-operative complications. Fifty-one patients (49%) had a relapse. The median follow-up was 55 months. Twenty-six patients remain alive and 78 patients have died. The overall 5-year survival rate was 32%, with an estimate median survival time of 28 months; according to the pathologic stage, the survival data were 52.2%, 30% and 15.3% for stage I, II and III, respectively (P < 0.001). The 5-year survival was 41% in patients without SCLC after chemotherapy. CONCLUSION: As with non-small cell lung cancer, survival following surgery and chemotherapy clearly correlates with the stage. At present, it is not clear whether surgery is truly effective for patients with SCLC. In our experience, the complete elimination of small cell lung cancer is associated with an improvement in survival (41% at 5 years).

Adult↗

PubMed1998

Ultrarapid high-dose course of prophylactic cranial irradiation in small-cell lung cancer: evaluation of late neurologic morbidity in 16 long-term survivors.

Despite the reduction in the incidence of brain metastases following prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), the use of this modality is still controversial due to the lack of improvement in survival and the appearance of neurotoxicity in long-term survivors. Moreover, the optimum dose, fraction size, and timing are not known. From 1980 to 1988, 70 patients with limited stage SCLC underwent PCI after or during multimodality treatment of their primary tumor. Most of these patients (75.7%) received an unconventional ultrarapid high-dose course of 17 Gy in two fractions over 3 days. Long-term (range 60-138 months) survivors (n = 16) were invited to have a complete neurological evaluation including computed cranial tomography (CCT), 99mTc-HMPAO single photon emission computerized tomography (SPECT) scan, electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychometry. Delayed neurologic complications or psychometric impairment was observed in 46% of patients. One or more abnormalities were detected by CCT in all patients, and the presence of neurologic complications seemed to correlate with periventricular and subcortical white matter changes. A strong correlation was found between CCT and SPECT periventricular white matter changes. Although the incidence of late neurologic toxicity following this rapid course of irradiation was high, clinical findings were less severe than expected, and all the patients were capable of self-care.

Adult↗

PubMed1997

Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase II study.

PURPOSE: The nucleoside analog, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC). Its combination with cisplatin in preclinical models suggested synergy between the two drugs. The aim of the study was to evaluate the clinical efficacy and toxicity of the cisplatin-gemcitabine combination in advanced NSCLC. PATIENTS AND METHODS: Forty-eight consecutive previously untreated NSCLC patients entered the trial from January to June 1994. The median age was 60 years (range, 37 to 70) and performance status (PS) was 0 or 1; 22 patients had unresectable stage III disease (21 stage IIIB and one stage IIIA) and 26 had stage IV disease. Gemcitabine 1 g/m2 was administered weekly (days 1, 8, and 15) followed by a 1-week rest and cisplatin 100 mg/m2 on day 2 of each 28-day cycle. Survival and response were determined in accordance with the intention-to-treat principle in all enrolled patients. RESULTS: Of 48 assessable patients, one (stage IV) had a complete response (CR) and 25 achieved a partial response (PR). The overall response rate was 54% (95% confidence interval [CI], 40% to 68%). Thrombocytopenia was the main side effect, with 52% of patients experiencing grade III to IV toxicity, which was usually short-lived and responsible for the omission of gemcitabine administration on day 15 in 50% of chemotherapy courses. The median survival time was 61.5 weeks (95% CI, 40 to 71). CONCLUSION: The combination of gemcitabine and cisplatin induced a high response rate in both stage IIIB and IV NSCLC, with modest side effects. The regimen deserves further careful evaluation in a phase III prospective randomized trial.

Adult↗

PubMed1996

Mitomycin C, vinblastine, and carboplatin regimen in patients with nonsmall cell lung cancer. A phase II trial.

BACKGROUND: The mitomycin C, vinblastine, and cisplatin (MVP) combination is one of the most frequently used in the palliative setting, but it produces considerable toxicity. Carboplatin and cisplatin have different patterns of toxicity. The goal of this study was to evaluate a combination similar to MVP, using carboplatin instead of cisplatin to render it more feasible in an outpatient setting. METHODS: Inclusion criteria for this study included: inoperable patients or patients relapsing after previous surgery, with nonsmall cell lung carcinoma (NSCLC), a performance status (PS) > 50%, and no previous chemotherapy. The chemotherapy regimen included carboplatin, 300 mg/m2 on Day 1; mitomycin, 8 mg/m2 on Day 1; and vinblastine, 4 mg/m2 on Days 1, 8, and 15 (on Day 15 vinblastine was delivered only in the first cycle) (MVC) every 3 weeks for at least 3 cycles. RESULTS: From August 1991 until August 1994, 70 patients entered the trial. All were evaluable for toxicity and response. The median age was 62 years (range, 40-73 years). The male/female ratio was 60:10 (86%:14%); the ratio of Stage III to Stage IV disease was 26:44 (37%:63%); and the ratio of PS > 70 to < or = 70 was 49:21. A total of 296 cycles (median, 4 [range, 1-6 cycles] per patient) were delivered, 280 of 296 (95%) in an outpatient setting with only 4 patients requiring hospitalization for treatment delivery. Overall response rate (RR) was 38.6% (95% confidence interval [CI], 27-51%) (1 complete response, 1.5%; 26 partial responses, 37.1%). Median duration of response was 9.8 months (range, 2-27 months). In Stage III patients the RR was 42% and in Stage IV patients it was 34%. Overall median survival was 9.5 months (95% CI, 6.8-15.3 months). Survival at 1 year was 39% (standard error [SE] 3.6%) and was 11% at 2 years (SE 3.6%). In Stage III patients median survival was 13 months and the 1-year survival rate was 54% (SE 10%); Stage IV patients had a median survival of 7.4 months and a 1-year survival rate of 28% (SE 7%). Delivered dose intensity was: carboplatin, 71%; vinblastine, 60%; and mitomycin C, 77% of the planned dose intensity. The back calculation of carboplatin area under the curve (AUC) with Calvert's formula and with the Cockcroft-Gault glomerular filtration rate estimation, showed a median AUC value of 4 (range, 2-8). Using the more precise Chatelut formula, AUC was again 4 (range, 2-7). Hematologic toxicity was the major side effect; Grades 3 and 4 leukopenia were observed in 34% and 6% of patients, respectively, and Grades 3 and 4 thrombocytopenia in 25% and 4% of patients, respectively. Grade 2 infection occurred in 10% of patients, with only 1 case of sepsis; severe constipation and Grade 2 alopecia occurred in only 1 patient; and no case of higher than Grade 1 nephrotoxicity was observed. No pulmonary toxicity was observed. Compliance with treatment was good with only one patient refusal after the first cycle. CONCLUSIONS: Chemotherapy for advanced NSCLS is still controversial, because effectiveness in terms of RR and symptom control must be weighed against treatment toxicity and costs. From our study it appears that MVC is easy to deliver in an outpatient setting, and has good patient compliance, low toxicity profile, and promising RR and response duration. The substitution of carboplatin for cisplatin in regimens for advanced NSCLC should be considered.

Adult↗

PubMed1996

Pre-operative chemoradiotherapy in non-small cell lung cancer stage III patients. Feasibility, toxicity and long-term results of a phase II study.

The aim of this study was to evaluate the feasibility, the response rate and the effect on survival of full dose polychemotherapy delivered concurrently with bifractionated radiotherapy at a radical dose, in a subset of patients with marginally resectable or unresectable stage IIIA-B non-small cell lung cancer (NSCLC). Treatment consisted of two courses of cisplatin 100 mg/m2 for 1 day plus etoposide 120 mg/m2 for 3 days delivered from day 1 to day 22, plus radiotherapy delivered in two cycles of 2560 cGy each from day 3 to day 12 and from day 24 to 33 (total dose 5120 cGy in 31 days). The daily dose was 320 cGy in two equal fractions. After surgery, three additional courses of cisplatin plus etoposide were planned. From February 1988 to June 1991, 39 patients with stage III NSCLC (19 were judged as having marginally resectable, 20 as having unresectable disease) were entered into the study. Out of 39 patients (22 squamous cell carcinoma, 17 adeno/large cell carcinoma), 24 had stage IIIa (62%) and 15 stage IIIb (38%). Median PS was 80 (70-90). A total of 78 (74 evaluable) concurrent cycles of pre-operative chemoradiotherapy were delivered. The prominent side-effect was leucopenia: leucopenia > or = grade 3 at nadir occurred in 20 cycles (27%), thrombocytopenia > or = grade 3 at nadir in seven cycles (9%), 19 patients (54%) had a treatment delay of 1 week between the two cycles. Other important toxicities were sepsis in 5 patients (13%), oesophagitis > grade 2 in 9 patients (23%) and pneumonitis in 5 patients (13%). The response rate was 67% (6 CR (complete response), 16%; 19 PR (partial response), 51%). A resection was subsequently performed in 20 (51%) patients: 14 out of 19 marginally resectable (74%) and 6 out 20 initially unresectable (30%) patients. One other patient had an exploratory thoracotomy. Surgical specimens were tumour-free in 3 patients (14%); in 8 patients (38%) only microscopic tumour was found, and in 10 (48%) macroscopic residual tumour was found. Out of 23 patients attaining a CR, 5 relapsed locally and 11 only distantly. At present, with a follow-up ranging from 64 to 90 months, 34 patients have died, 1 is alive with recurrent disease and 4 (17%) are alive without evidence of disease. Median survival was 16 months, with 18% 3-year survivors and 13% 5-year survivors. Resected patients had a median survival of 21 months, versus 10 months for unresected patients (P = 0.01). No significant difference was evident between stage IIIa and stage IIIb patients.

Adult↗

PubMed1996

Paclitaxel and carboplatin: a phase I study in advanced non-small cell lung cancer.

In the treatment of non-small cell lung cancer paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has significant activity and carboplatin has single-agent activity comparable with that of cisplatin, with less pronounced nonhematologic toxicity. The optimal doses of paclitaxel and carboplatin in combination have not been determined. We designed a phase I study combining a fixed paclitaxel dose of 175 mg/m2, administered either by 3- or 1-hour infusion, with escalating doses of carboplatin given every 4 weeks. The starting carboplatin dose was 175 mg/m2, with planned dose increases in increments of 25 mg/m2. The primary study objective was to find the maximum tolerated dose of the combination. Secondary objectives were to determine the toxicity profile, response rate, and feasibility of a 1-hour paclitaxel infusion with steroid premedication delivered only 1 hour before the paclitaxel infusion. Eligibility criteria included age 18 to 75 years, no prior chemotherapy, stage IIIB to IV disease, Eastern Cooperative Oncology Group performance status 0 to 2, no second tumors, measurable or evaluable disease, and informed consent. We achieved a carboplatin dose level of 300 mg/m2 without reaching the maximum tolerated dose. The dose-limiting toxicity was granulocytopenia. However, only one patient had a neutrophil count less than 500/microL during the first cycle. Other toxicities during the first and remaining 73 delivered cycles were mild to moderate. Only one patient had treatment delayed, and no dose reductions were necessary. Of 22 patients entered, 19 were evaluable for response (two were not evaluable and one was too early to evaluate). Six partial responses (31%; 95% confidence interval, 13% to 57%), five (26%) stable diseases, and eight (42%) disease progressions were observed. No additional side effects were observed with the 1-hour paclitaxel infusion and single-dose steroid premedication 1 hour before chemotherapy. The study will continue until the paclitaxel/carboplatin maximum tolerated dose is reached.

Adolescent↗

PubMed1994

Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo.

BACKGROUND: The standard treatment for advanced (stage III and IV) head and neck squamous cell carcinoma (i.e., surgery with postoperative radiotherapy in operable patients and radiotherapy alone in inoperable patients) has had poor results. A series of randomized trials of induction chemotherapy have up to now failed to demonstrate an improvement in survival. PURPOSE: This trial was designed to determine whether intensive induction chemotherapy administered before loco-regional treatment would improve survival of patients with advanced disease. METHODS: Patients had previously untreated, advanced nonmetastatic (stages III and IV) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and paranasal sinuses. The study design was a randomized, multi-institutional, phase III trial. Eligible patients (n = 237) were randomly assigned to receive either initial chemotherapy (cisplatin and infusional fluorouracil) followed by loco-regional treatment (group A, n = 118) or loco-regional treatment alone (group B, n = 119). For operable patients (group A, n = 34; group B, n = 32), loco-regional treatment included resection followed by adjuvant radiotherapy. For inoperable patients, radical irradiation was performed with a planned dose of 65-70 Gy to involved areas. A dose of 45-50 Gy was also planned to the uninvolved neck or postoperatively. The statistical (log-rank) test was performed no earlier than 2 years after the randomization of the last patient. RESULTS: Seventy-one patients (60%) in group A and 67 patients (56%) in group B were considered free of disease after they completed the treatment sequence. The analysis of time to distant metastases showed an advantage for group A patients. (Respective 2- and 3-year values for inoperable patients were 15% and 24% for group A versus 36% and 42% for group B, P = .04; only one operable group A patient had distant metastases after 49 months versus 26% [2 years] and 31% [3 years] for operable group B patients, P = .01.) For inoperable patients, the combined treatment was significantly associated with an increase in complete remission rate (group A, 44%) as compared with radiotherapy alone (group B, 30%) (P = .037). Inoperable patients also benefitted from induction chemotherapy in terms of disease-free survival (49% and 34% for group A versus 28% and 26% for group B; P = .06) and of overall survival (30% and 24% for group A versus 19% and 10% for group B; P = .04). CONCLUSIONS: When all 237 randomly assigned patients were analyzed, there were no significant differences in the two treatment strategies in loco-regional failure or in disease-free or overall survival, although the development of distant metastases was reduced. For operable patients, the only benefit from neoadjuvant chemotherapy was a significant reduction in the incidence of distant metastases. For inoperable patients, neoadjuvant chemotherapy improved local control, decreased the incidence of distant metastases, and improved the complete remission rate and overall survival. IMPLICATIONS: Confirmatory studies with effective chemotherapy regimens delivered for an adequate number of cycles are required.

Adult↗

PubMed1994

Bleeding peptic ulcer occurring in hospitalized patients: analysis of predictive and risk factors and comparison with out-of-hospital onset of hemorrhage.

We reviewed 84 consecutive cases of peptic ulcer hemorrhage, which occurred, in an area of 270,000 people, from 1986 to 1988, in patients already hospitalized for other diseases (in-bleeders). These subjects were compared with a prospective series of 386 patients who initially bled as out-patients and were then admitted (out-bleeders). Of 84 hemorrhages in hospitalized patients, 41 followed major surgery, while 43 were associated with other severe conditions. Bleeding site was duodenal in two thirds. Mean age was 67 +/- 15 years versus 59 +/- 15 among out-bleeders. Fifty percent of in-bleeders had recently received nonsteroidal antiinflammatory drugs (NSAIDs), and one third were on anticoagulants and 10% on corticosteroids; in 39 (46%) bleeding was shown to be persistent or recurrent, 5 (5.9%) underwent endoscopic and 18 (21%) surgical therapy; 29 died (34%). The corresponding figures among out-bleeders were: further bleeding 80 (20.7%), endoscopic therapy 12 (3.1%), surgery 25 (6.5%), deaths 17 (4.4%). As regards in-bleeders, only active bleeding and endoscopic stigmata emerged as statistically significant risk factors for further bleeding. The latter was shown to be significantly related to mortality. The most relevant finding was, however, that NSAIDs and anticoagulants, in association with stress and aging, are very frequently involved in peptic ulcer bleeding of hospitalized patients. The fatal outcome of one third, despite all available treatments, highlights the importance of prevention against drug- and stress-related mucosal damage in in-patients suffering from severe diseases.

Aged↗

PubMed1994

The effects of prolonged cardiopulmonary bypass on cell-mediated immunity.

Studies of T-cell subsets (CD3+, CD4+, CD8+, CD8+ CD57+ cells), lymphocyte response to concanavalin A (Con A), phytohaemoagglutinin (PHA) and the alterations of white cell membranes shown by scanning electronic microscope (SEM) in 51 patients who underwent cardiac operation were performed. Out of these 51 unselected patients, for 16, duration of CPB was < or = 110 min (group A), while for the other 35 (group B) it was prolonged (> 110 minutes). Although variations of the lymphocyte subset observed between groups A and B were slightly significant (p < 0.05 before CPB and on postoperative day 7), the T-cell reactivity in group B in comparison to that of group A did not normalize by postoperative day 7 regardless of stimulation with PHA or with Con A. With the use of the SEM, the folded aspect of lymphocyte surface decreased after surgery in about 71% (group A) and 78% (group B) of the observed cells. The outcome of the immunological effects given by our studies could have been due to an elongated CPB even if there need to be taken into consideration multifactorial influences, i.e. biological, pharmacological and hormonal hypotheses, and rapid changes in CPB-micro-environment.

Cardiopulmonary Bypass↗

PubMed1994

[Energy expenditure during a pregnancy complicated by post-traumatic coma: analysis of 2 clinical cases].

OBJECTIVE: To analyze the measured resting energy expenditure, the clinical evolution and the nutritional therapy of two pregnant women complicated by post-traumatic coma and sepsis. DESIGN: Clinical study. SETTING: The ICU of Neurosurgery in Regional Hospital in Italy. PATIENTS: Two subjects with head trauma due to a motor vehicle accident. METHOD: The resting energy expenditure was measured (M-REE) by indirect calorimetry by oxygen consumption (VO2) and carbon dioxide production (VCO2). Values were controlled in patients with a hemodynamic stability every 4 hours. Predicted REE (P-REE) was calculated according to the Harris-Benedict formula. A total parenteral nutrition (1.2-1.3 x M-REE) composed of dextrose (70-80% of total caloric amount) and fat (20-30%) was infused in both the subjects. As an average 12-15 g of nitrogen were infused daily. RESULTS: VO2 and VCO2 increased during the study (case 1: from 225 +/- 33 to 325 +/- 35 ml/min; p < 0.02; LR: p < 0.0001; VCO2: from 170 +/- 24 to 289 +/- 23 ml/min; p < 0.0001. Case 2: VO2: from 239 +/- 22 to 315 +/- 35 ml/min; p < 0.05; LR: p < 0.01. VCO2 from 177 +/- 31 to 247 +/- 22 ml/min; p < 0.05; LR: p < 0.001). M-REE/kg increased with statistical significance during the study (case 1: from 23.6 +/- 4.1 to 34.1 +/- 4.3, p < 0.05, LR: p < 0.005; case 2: from 23.7 +/- 5.8 to 33.4 +/- 7.7, p < 0.05, LR: p < 0.05). A physiological variation in oxidative capacity on nutritional substrates was reported throughout the study. CONCLUSION: Sepsis and miscarriages following trauma seem to be the cause in an increase of the energy expenditure rather than pregnancy itself. However our observations must be viewed with caution because they are based on a small number of patients.

Abortion, Spontaneous↗

PubMed1994

[Gastric pH changes during and after extracorporeal circulation. What is its clinical meaning?].

OBJECTIVE: To determine the relationship between gastric pH (pHm) and several other indices of blood perfusion in patients undergoing cardiopulmonary bypass (CPB). To evaluate the importance of pHm as a prognostic index for elective cardiac surgery. DESIGN: Prospectives study. SETTING: Cardiac surgery ICU of a Regional Hospital in Italy. PATIENTS: Nineteen patients were sequentially studies in a 4-month period. METHOD: Before anesthetic induction, a pH probe incorporated in the tip of a nasogastric tube (GrapHprobe SH, GrapHometer, Zinetics Medical, USA) was inserted in the stomach. Results, collected during the CPB and in the postoperative period until 1 hour after extubation, were compared to the peripheral tissue perfusion and oxygenation data (transcutaneous: PtcO2), hemodynamic variations (Swan-Ganz catheter), pharyngeal temperature, and blood gases. RESULTS: No significant variations of pHm were reported during the study. Significant relations were found only after surgery between pHm and PaO2 (p < 0.001), hemoglobin (p < 0.001), and blood pH (p < 0.05). No statistical correlations were reported between pHm and hemodynamic variations. CONCLUSIONS: Although a significant variation of peripheral and pulmonary vascular resistance and transcutaneous oxygenation was reported throughout the study, no correlations were found to pHm. At present it is not possible to confirm the importance of pHm as a prognostic index for elective cardiac patients, even though it is necessary to examine whether the additional data of pHm variation could be considered a true marker of visceral perfusion.

Aged↗

PubMed1994

Acute renal failure in the patient undergoing cardiac operation. Prevalence, mortality rate, and main risk factors.

A total of 775 consecutive patients who survived the first 24 hours after cardiac operation were prospectively studied to assess the prevalence, mortality rate, and main risk factors for development of new acute renal failure. Normal renal function before operation (serum creatinine level less than 1.5 mg/dl) was registered in 734 (94.7%) patients. Of these, 111 (15.1%) showed a postoperative renal complication including 84 (11.4%) classified as renal dysfunction (serum creatinine level between 1.5 and 2.5 mg/dl) and 27 (3.7%) as acute renal failure (serum creatinine level higher than 2.5 mg/dl). The mortality rate was 0.8% in normal patients, 9.5% in patients with renal dysfunction, and 44.4% when acute renal failure developed (p < 0.0001). Indeed, the renal impairment proved to be an independent predictor of mortality (p < 0.001), along with the infective (p < 0.001), gastrointestinal (p < 0.001), and cardiovascular (p < 0.05) complications. Multivariate analysis identified the following variables as independent risk factors for postoperative renal impairment: use of intraaortic balloon pump (p < 0.0001), need for deep hypothermic circulatory arrest (p < 0.005), low-output syndrome (p < 0.005), advanced age (p < 0.005), need for emergency operation (p < 0.025), and low urinary output during cardiopulmonary bypass (p < 0.05). The 41 patients (5.3%) with preoperative renal failure showed a significantly higher morbidity and mortality rate than those without renal complications before operation. We conclude that in patients undergoing cardiac operation without preexisting renal dysfunction the likelihood of severe renal complications is reasonably low, but the associated mortality remains high. A prominent role in the development of postoperative acute renal failure must be recognized for preoperative, intraoperative, and postoperative hemodynamic factors, whereas cardiopulmonary bypass seems to be of lesser importance in this respect.

Acute Kidney Injury↗

PubMed1993

Granulocyte-macrophage colony-stimulating factor increases dose intensity of chemotherapy in small cell lung cancer. Relationship between clinical results, peripheral blood cell modifications, and bone marrow kinetics.

BACKGROUND: Until now, no dose-response correlation has been clearly defined in small cell lung cancer (SCLC). METHODS: Forty-one consecutive patients with SCLC entered this study, 21 (limited [L]/extensive [E] = 10/11) patients (group A) received cisplatin 60 mg/m2, etoposide 120 mg/m2 x 3, and escalating epirubicin (5 mg/m2) starting from 45 mg/m2, every 3 weeks for six courses. RESULTS: The maximum tolerated dose (MTD) was reached at epirubicin 60 mg/m2. In 15 (L/E = 9/6) patients (group B), who were submitted to the same combination plus granulocyte-macrophage colony-stimulating factor (GM-CSF) 10 micrograms/kg on days 4 to 14, the MTD was reached at the epirubicin dose of 70 mg/m2. In five (L/E = 4/1) patients (group C) treated as in group B, but with a GM-CSF priming from day -17 to -7 before the first cycle, the MTD was again at 70 mg/m2. Group A patients received 73% of the planned cycles; groups B and C, 86% (P < 0.015). Twenty-five percent of group A cycles versus 6% of groups B and C were delayed (P = 0.0018). The chemotherapy dose was reduced in 15% versus 1.5% of cycles (P = 0.0072). A significant difference was observed in the delivered dose intensity (DI) and in the relative DI with an increase of 29% for cisplatin and etoposide (P < 0.0005; P = 0.0017) and of 63% for epirubicin (P < 0.0000). In group A, the response rate was 72% (24% complete response [CR]), and in groups B and C, 95% (40% CR). Bone marrow myeloid precursor (BMMP) proliferative activity was determined in 21 patients after in vivo bromodeoxyuridine infusion. In GM-CSF-treated patients the production rate evaluated before the starting of the second, fourth, and fifth cycle was significantly higher than the corresponding value of the first cycle. CONCLUSIONS: GM-CSF induces a significant increase of dose intensity by a long-lasting and cumulative enhancement of BMMP proliferation.

Aged↗

PubMed1993

Bone marrow myeloid cell kinetics during treatment of small cell carcinoma of the lung with chemotherapy not associated and associated with granulocyte-macrophage colony-stimulating factor.

Information on the kinetics of bone marrow (BM) myeloid precursors (BMMP) is required for integrating cancer chemotherapy with granulocyte-macrophage colony-stimulating factor (rhGM-CSF), with the aim of reducing neutropenia. Using bivariate flow-cytometric analysis of the in vivo incorporation of bromode-oxyuridine (BUDR) vs DNA content we have studied the kinetics of BMMP in 21 patients with SCLC during the first of six chemotherapy courses (etoposide, epirubicin, and cis-platinum, days 1-3, every 21 days), given alone (eight patients) or followed by rhGM-CSF (10 micrograms/kg/day s.c., days 4-14) as BM rescue (eight patients) or both preceded (days -17 to -7, as BM priming) and followed by rhGM-CSF (five patients). At 11-14 days after the start of these therapies there was an increase in the baseline proliferative activity of proliferating BMMP and a shortening in the time needed by the metamyelocyte to mature and to leave the marrow. Both effects were greater and were maintained to a significantly greater degree a week later in patients who received chemotherapy plus rhGM-CSF rescue than in those who received chemotherapy alone or rhGM-CSF priming alone. At day 11-14 the pretreatment median cell production rate of pBMMP was increased by 340%, 150%, and 183% and the maturation time was reduced by 80%, 45%, and 57%, respectively, in the three groups. A week later, the corresponding figures were 206%, 111%, and 157% and 50%, 18%, and 45%. Hence, an identical rhGM-CSF schedule is more effective in increasing the neutrophil production by BMMP when given following chemotherapy as BM rescue than before it as BM priming. In both the rescue and the priming schedule, the increase in proliferative activity of BMMP just at the end of rhGM-CSF stimulation was linked to both an increase in the labeling index and a reduction in duration of S-phase (TS), while a week later it was linked solely to reduction in TS. This could actually reduce one of the two kinetic targets of subsequently administered cytostatics, i.e., a high LI and a long time spent in S phase. From this study, accurate kinetic data can be obtained with the in vivo BUDR technique that are useful in scheduling rhGM-CSF.

Aged↗

PubMed1993

Study of the expression and function of the tumour-associated antigen CaMBr1 in small cell lung carcinomas.

The expression of the epithelial antigen recognised by the MBr1 monoclonal antibody (CaMBr1) was studied on 161 small cell lung carcinoma (SCLC) biopsies. A correlation between the marker expression and the overall survival of the patients was found. To investigate the possible role of CaMBr1 in tumour aggressiveness, the in vivo and in vitro growth capabilities of different SCLC cell lines, in relation to the antigen expression, were analysed. The CaMBr1-positive cell lines displayed a higher growth potential in comparison to CaMBr1-negative cells. The biochemical nature of CaMBr1 was analysed in terms of enzyme sensitivity, molecular weight and comparison with other glycoproteins expressed by SCLC cells. The results indicated the trypsin sensitivity of the molecule, and sialic acid hiding of the CaMBr1 epitope. The increase of MBr1 reactivity after neuraminidase treatment suggests that the CaMBr1 epitope expressed in the SCLC cell line is carried by a sialoglycoprotein.

Animals↗

PubMed1993

Epirubicin, methotrexate and bleomycin in the management of recurrent squamous cell head and neck cancer. A GSTTC randomised phase II study.

53 patients with squamous cell carcinoma of the head and neck recurrent after initial treatment were entered into a phase II trial of the epirubicin, methotrexate and bleomycin (EMB) combination. The primary objective of the study was to evaluate the activity of this combination. Compliance to EMB and the possible non-cross-resistance to previous cisplatin-containing chemotherapy were secondary objectives. In order to avoid patient selection bias, the study involved randomisation between EMB and a cisplatin-methotrexate-bleomycin (DMB) combination (with EMB: DMB = 2:1). 23 out of 53 (43% +/- 13) EMB patients showed an objective response, lasting a median of 12 (range 4-39) weeks; interestingly, 5 out of 14 (36% +/- 25) patients pretreated with cisplatin plus 5-fluorouracil responded to EMB. The treatment compliance was good and a median of three courses was delivered. No patient refused the treatment after the initial cycle. Leukopenia (47%) and oral mucositis (42%) were the main side effects. DMB produced a response rate of 33% +/- 18 with a median duration of 5 (4-13) weeks. None of the patients previously treated with cisplatin plus 5-fluorouracil responded. 5 patients refused the treatment after the first cycle and a median of two cycles (0-5) was delivered. In conclusion, EMB produced results similar to cisplatin-containing regimens, with a mild to moderate toxicity and a good compliance; the possible non cross-resistance with cisplatin plus 5-fluorouracil deserves further evaluation.

Adult↗

PubMed1993

A pilot study of concomitant radiation and chemotherapy in patients with locally advanced head and neck cancer.

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.

Adenocarcinoma↗

PubMed1993

The pericardium reinforced suture annuloplasty: another tool available for mitral annulus repair?

From May 1985 to May 1992, 169 patients underwent surgery for mitral valve repair. In 87% of these patients, the valve reconstruction involved the mitral annulus. At the beginning, in an effort to preserve systolic movement of the annulus and avoid the implant of prosthetic materials inside the heart, we mainly used simple suture annuloplasty in 66 patients. When we reoperated upon three patients only a few months after reconstruction of the mitral valve for a dehiscence of the suture annuloplasty, we decided to perform ring annuloplasty with the Carpentier ring in 23 patients. Though we have not seen any problems with the Carpentier ring in our series, we performed a suture annuloplasty reinforced with a strip of autologous pericardium to eliminate all prosthetic material. Since introducing this technique in 1989, we have used this annuloplasty in 58 patients. We have not observed any dehiscence of the suture or other complications related to this procedure. Three patients with a pericardial annuloplasty underwent reoperation for other reasons; the autologous pericardium was perfectly attached to the annulus, covered by a smooth layer of fibrous tissue without calcification. After this encouraging initial experience, we believe that long-term follow-up is necessary to confirm that autologous pericardium is an effective method of mitral annulus repair.

Heart Valve Diseases↗