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A Gentile

Publications and source records attributed to A Gentile.

At least 55 records · Page 3Linked to original sources
PubMed1997

A phase I-II trial of fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer.

We conducted a phase I-II study with escalating paclitaxel doses plus carboplatin at a fixed dose for previously untreated patients with advanced ovarian cancer in order to define the maximum tolerated dose. Eligible for the study were women with a histologically confirmed diagnosis of ovarian cancer stage III-IV according to the FIGO classification. In the first phase of the study, 6 patients were allocated escalating paclitaxel doses with fixed-dose carboplatin in order to establish the maximum tolerated dose. The starting dose of paclitaxel was 150 mg/m2 given after carboplatin (300 mg/m2) every 4 weeks for a total of six courses. The paclitaxel dose step was 25 mg/m2 up to 250 mg/m2. The study then progressed to a phase II trial using the maximum tolerated paclitaxel dosage reached during the escalating dose phase. A total of 27 patients entered phase I and 23 phase II. Neurotoxicity was observed in 47 patients (94%; 29 grade 1, 17 grade 2, 1 grade 3, according to the WHO classification). The intensity of neurotoxicity tended to be dose related: out of the 15 patients who received < or = 200 mg paclitaxel, a total of 14 grade 1, but no grade 2 or 3 neurotoxicities, were observed. The frequency of grade 1, 2 and 3 neurotoxicity was 15, 17 and 1, respectively, in the 35 women who received > or = 225 paclitaxel +300 mg carboplatin. There was no clear relationship between median WBC and platelet nadir and dose level. Among other toxicities, alopecia was observed in all 50 cases, hypersensitivity in two (4%) and myalgia in 41 (82%; 34 grade 1 and 7 grade 2). These frequencies tended to increase with the dose, but the relationship was not statistically significant. The overall response rate was 78% (39/50) with a complete response rate of 62% (31/50). In conclusion, this study suggests that carboplatin and paclitaxel can be administered safely to patients with advanced ovarian carcinoma. The maximum dose reached was 250 mg/m2 paclitaxel and 300 mg/m2 for carboplatin, but from a clinical point of view the maximum paclitaxel dose we would consider safe is 225 mg/m2.

Adult↗
PubMed1997

Distribution of capsular types and penicillin-resistance of strains of Streptococcus pneumoniae causing systemic infections in Argentinian children under 5 years of age. Streptococcus pneumoniae Working Group.

Streptococcus pneumoniae (SPN) is the most common cause of invasive infections in children, with high levels of mortality in developing countries. An increase in frequency of penicillin-resistant strains is reported in most parts of the world. A study was undertaken in Argentina and 5 other countries of the region, to determine the type distribution and penicillin resistance rate of SPN isolated from invasive infections in children less than 5 years old. Between June 1994 and March 1996, a total of 505 SPN isolated from sterile sites were collected from 15 hospitals located in 9 cities of different geographic areas. Clinical and epidemiological data from 443 children were analyzed. Sixty five percent SPN were isolated from children less than 2 years old. Pneumonia was the clinical diagnosis in 58% of the cases, meningitis in 22%, and sepsis in 10.6%. Isolates were recovered from blood (51.2%), pleural fluid (22.7%), CSF (20.7%), and other sterile sites (5.4%). Thirty different pneumococcal capsular types were identified and the 10 most frequent in descending order were: 14, 5, 1, 6A/6B, 7F, 9V, 19F, 19A, 16F y 23F, representing 89.3% of the total. Overall, 13.1% of isolates showed intermediate resistance to penicillin while 11.3% showed high resistance. Lethality was 8.8%, without correlation with penicillin-resistance and/or type. These result should be used in selecting the optimal combination of specific types for a conjugate vaccine, useful in children less than 2 years old and for considering therapeutic strategies for invasive pneumococcal infections.

Argentina↗
PubMed1997

Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen with high activity and low cardiotoxicity in advanced breast cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of paclitaxel over 3 hours with a fixed dose of epirubicin, to investigate the plasma pharmacokinetics of this combination, and to evaluate the toxicity and the activity in previously untreated metastatic breast cancer patients. PATIENTS AND METHODS: Fifty patients with metastatic breast cancer, measurable disease, and normal left ventricular ejection fraction (LVEF) were eligible. Epirubicin was administered as an intravenous (I.V.) bolus at the fixed dose of 90 mg/m2 before the infusion of paclitaxel over 3 hours. The initial dose of paclitaxel was 135 mg/m2 and was increased by 20 mg/m2 in subsequent cohorts of six patients until dose-limiting toxicity (DLT). Plasma pharmacokinetics of paclitaxel and epirubicin was performed at cycle 1 in at least two patients per dose level of paclitaxel (175 up to 225 mg/m2). RESULTS: The DLT of this combination was febrile neutropenia in two of eight patients who received paclitaxel at 225 mg/m2. The mean peak plasma concentration of paclitaxel ranged between 5.1 and 6.2 micromol/L at doses of 175 to 225 mg/m2. The concentration of epirubicinol decreased from 47.3 +/- 9.4 to 37.9 +/- 7.5 ng/mL in patients treated with paclitaxel 175 and 225 mg/m2. The most relevant toxicity was grade 4 neutropenia (61% of all courses). The pharmacokinetic data of paclitaxel, in particular the time above the threshold level of 0.05 micromol/L, were not significantly related to myelosuppression. Cardiac toxicity was mild: three patients (6%) developed mild congestive heart failure that was responsive to therapy. Among 49 assessable patients, 41 responses (84%; 95% confidence interval [CI], 70% to 92%) were observed, and nine (18%) of these were complete. CONCLUSION: Our study demonstrates that (1) the MTD is epirubicin 90 mg/m2 and paclitaxel 200 mg/m2; (2) no clear relationship exists between pharmacokinetic data of paclitaxel and myelosuppression, while the increase in the dose of paclitaxel is associated with a reduction in epirubicinol plasma levels; and (3) the association is feasible, with low cardiotoxicity, and has a high activity in metastatic breast cancer.

Adult↗
PubMed1997

Doxorubicin and paclitaxel (sequential combination) in the treatment of advanced breast cancer.

Based on preclinical data, we designed a phase I/II clinical trial to determine the efficacy and toxicity of doxorubicin followed by paclitaxel in the treatment of advanced breast cancer (either untreated or relapsed after adjuvant therapy). In the phase I dose-finding study, 19 enrolled patients received bolus doxorubicin (50 mg/m2) and, after a 16-hour interval, a three-hour infusion of paclitaxel in escalating doses from 130 to 250 mg/m2, increased by 30-mg/m2 increments for each dose-level group. The first dose level group (paclitaxel 130 mg/m2) included three patients. The other dose level groups included four patients. Treatment was repeated every three weeks for a maximum of eight cycles. The paclitaxel dose was escalated to 250 mg/m2 without reaching the maximum tolerated dose. In the 128 cycles assessable for toxicity, there were no relevant clinical signs or symptoms of cardiotoxicity. This absence of significant cardiotoxicity required confirmation in a phase II trial. Since a maximum tolerated dose of paclitaxel had not been reached during the first study and an increasing risk of neutropenia and peripheral neurotoxicity was feared if doses continued to escalate, a phase II confirmatory study was begun to evaluate treatment with fixed doses of doxorubicin (50 mg/m2) and paclitaxel (220 mg/m2), using the same schedule and interval as in phase I. The 13 patients enrolled in phase II received a total of 95 cycles of therapy; in 10 cycles (three patients) dose reductions were necessary because of toxicity. However, no significant clinical cardiotoxicity was observed in 12 of the 13 patients. One patient experienced an asymptomatic, transient decrease in left ventricular ejection fraction at a cumulative doxorubicin dose of 400 mg/m2. Overall clinical responses included 10 complete remissions (31.3%) and 15 partial remissions (46.9%) for an objective response rate of 78.1%. At 16 months' median follow-up, the median time to progression for all patients is nine months. The high response rate obtained in the phase I/II studies and, in particular, the absence of significant cardiotoxicity require confirmation in further clinical trials. To date, two confirmatory phase II trials are ongoing in our institutions.

Antibiotics, Antineoplastic↗
PubMed1997

Paclitaxel plus doxorubicin in breast cancer: an Italian experience.

Based on preclinical data, phase I/II clinical trials were performed at Istituto Oncologico Romagnolo (IOR) Operative Units (Medical Oncology Departments of Forlì, Rimini, and Ravenna, Italy) to determine the efficacy and toxicity of sequential administration of doxorubicin followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer that either had been previously untreated or that had relapsed after adjuvant therapy. In the phase I trial, 19 patients received bolus doxorubicin (50 mg/m2) followed after a 16-hour interval by paclitaxel (given at dose levels ranging from 130 to 250 mg/m2) by 3-hour infusion every 3 weeks, for a maximum of eight cycles. Paclitaxel doses were escalated in 30-mg/m2 increments if the maximum tolerated dose had not been reached in the previous dose level. Analysis of the 128 cycles assessable for toxicity demonstrated neutropenia (<500/microL) in 26 courses (20.3%), with no significant clinical events. No relevant clinical cardiotoxicity was observed. The paclitaxel maximum tolerated dose was not reached at the 250-mg/m2 dose level (no grade 3 or 4 extramedullary toxicity). In the IOR phase II trial, 13 patients were treated with fixed doses of both drugs (doxorubicin 50 mg/m2 and paclitaxel 220 mg/m2). Grade 4 neutropenia occurred in 39 of the 95 cycles, but was complicated by fever in only eight cycles (8.4%); three cycles required granulocyte colony-stimulating factor support. Peripheral neurotoxicity was the most common extramedullary side effect noted. Overall clinical responses in the IOR trials included 10 complete responses (31.3%) and 15 partial responses (46.9%), with an objective response rate of 78.1%. Comparison of these results with those obtained from a phase I trial using the opposite drug sequence showed comparable overall response rates, but IOR's sequence was associated with a higher complete response rate, as well as less frequent and less severe nonhematologic toxicity.

Adult↗
PubMed1997

Chemotherapy for relapsed head and neck cancer: paclitaxel, cisplatin, and 5-fluorouracil in chemotherapy-naive patients. A dose-finding study.

The aim of this trial was to identify the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered via a 3-hour infusion day 1, together with cisplatin 20 mg/m2/d days 1 to 3 and 5-fluorouracil 200 mg/m2/d bolus days 1 to 3 every 21 days. The prophylactic administration of colony-stimulating factors was not allowed. Twenty-three patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck previously treated with surgery and/or radiotherapy were accrued. None had received chemotherapy previously. No grade 3/4 hematologic toxicity at nadir or other limiting toxicities were recorded with paclitaxel at 100 to 135 mg/m2 (six patients, 26 courses). Seven patients (six evaluable, 22 courses) were treated with 160 mg/m2. Grade 4 neutropenia at nadir with fever lasting 3 days was observed in one patient. Nonhematologic toxicities, including temporary peripheral neuropathy, asthenia, myalgias, vomiting, and mucositis were generally mild. Three patients were treated with 180 mg/m2 (eight courses). Grade 4 neutropenia at nadir was recorded in all patients and was febrile in two. Seven patients (six evaluable, 23 courses) were treated with paclitaxel 160 mg/m2, cisplatin 25 mg/m2/d, and 5-fluorouracil 250 mg/m2/d. Grade 4 febrile neutropenia at nadir was recorded in one patient. One episode of grade 4 mucositis and two episodes of grade 3 diarrhea were also recorded. Overall, eight responses (38%) were observed. In conclusion, the combination of paclitaxel 160 mg/m2, cisplatin 25 mg/m2/d, and 5-fluorouracil 250 mg/m2/d for 3 consecutive days can be administered safely without growth factor support. This regimen merits further investigation in a phase II trial.

Adult↗
PubMed1997

Prolactin response to thyrotropin-releasing hormone as a guideline for cyclical mastalgia treatment.

METHODS: We studied a group of 36 fertile women affected with moderate-to-severe cyclical mastalgia (mean age: 26.0 years) showing a normal menstrual history and normal basal levels of circulating hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), progesterone (P), testosterone (T), dehydroepiandrosterone sulphate (delta HEAs), androstenedione (A). Using serial measurements of PRL plasma levels after an intravenous injection of thyrotropin-releasing hormone (TRH), (TRH test), patients were divided in two groups: 19 patients with abnormal PRL response to TRH and the remaining 17 with normal response. RESULTS: Bromocriptine treatment, 2.5 mg b.i.d. for 3-6 months, was effective in 73.6% of patients with abnormal TRH test and in 23.5% of patients with normal TRH test: the difference was statistically significant. On the other hand, 76.9% of patients with either normal TRH test or resistant to bromocriptine therapy had a favourable response to percutaneous progesterone and systemic non-steroidal antiinflammatory drugs (NSAIDs). CONCLUSIONS: These results seem to confirm the hypothesis that PRL response to TRH could be used to identify patients affected with cyclical mastalgia that are likely to benefit by bromocriptine treatment.

Adolescent↗
PubMed1997

[Current indications for esophageal transection with gastric devascularization in the treatment of hemorrhaging esophageal varices].

When endoscopic sclerotherapy fails or after recurrence, a surgical approach is necessary. Oesophageal transection is a rational and effective option, because, compared to the shunt, it does not change hepatic haemodynamics, it has lower operative mortality, particularly in emergency, and it does not complicate the surgical technique of a subsequent liver transplant. The authors report their own experience of 12 patients undergoing oesophageal transection out of a total 148 treated with endoscopic sclerotherapy for bleeding oesophageal varices, over a 5 year period. 4 patients were operated in emergency and 8 after haemorrhagic recurrence, 5 because of advanced hepatopathy and 3, young and Child A, because they were potential candidates for a liver transplant. Operative mortality has been nil, morbidity about 40% and the mean postoperative stay 15.4 days (range 10-21). In a mean follow up of 30 months haemorrhagic recurrence was 16.6% (2 cases); 2 patients died respectively 26 and 40 months after surgery.

Adult↗
PubMed1996

Phase II study of intensive chemotherapy with carboplatin, ifosfamide and etoposide plus recombinant human granulocyte colony-stimulating factor and sequential radiotherapy in locally advanced, unresectable non-small-cell lung cancer.

From June 1991 to August 1994, 61 patients with stage III unresectable non-small-cell lung cancer (NSCLC; 16 cases of stage IIIA with N2 bulky disease and 45 cases of stage IIIB) were treated with ifosfamide given i.v. at 3 g/m2 on day 1, carboplatin given i.v. at 200 mg/m2 on days 1 and 2, etoposide given i.v. at 120 mg/m2 on days 1-3 (ICE) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) given s.c. at 5 micrograms/kg on days 4-13. Chemotherapy was given every 3 weeks for up to three cycles and, unless the disease progressed, was followed by thoracic radiotherapy on the tumor volume (total dose 60 Gy) and mediastinum (40 Gy). All patients had measurable or evaluable unresectable disease and a performance status (Eastern Cooperative Oncology Group) of 0-1. Only 61% of the enrolled patients received the full program of chemoradiotherapy according to the study design. At the end of sequential chemo-radiotherapeutic treatment, 41% of the patients had an objective response (24 partial responses and 1 complete response), 31% showed no change and 28% had progressive disease. The response rate noted for patients in stage IIIA with N2 bulky disease and that recorded for patients in stage IIIB did not differ significantly. The median time to progression was 5.4 months and the median survival was 8.2 months, with the 1-year survival rate being 31%. Sites of progression were mostly intrathoracic. Haematological toxicity was the main side effect, with grade III-IV thrombocytopenia being reported in 24% of the 165 courses of intensive ICE chemotherapy given. Febrile neutropenia was described in six courses (three patients). Non-haematological toxicities and radiotherapy-related side effects were generally mild and easily manageable. In conclusion, in unresectable stage III NSCLC a short program of moderately intensified ICE chemotherapy with rhG-CSF protection followed by sequential radiotherapy failed to increase the percentage of objective responses and reached a median survival comparable with that previously achieved with standard doses.

Adenocarcinoma↗
PubMed1996

A Phase I/II study of paclitaxel and doxorubicin in the treatment of advanced breast cancer.

We designed a clinical study in which fixed doses of doxorubicin were infused by intravenous bolus 16 hours before escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, princeton, NJ) for the treatment of patients with advanced breast cancer, an interval selected to allow systemic clearance of doxorubicin before administration of paclitaxel in an outpatient setting. Courses of fixed-dose doxorubicin 50 mg/m2 by intravenous bolus and paclitaxel (doses escalated from 130 mg/m2 to 250 mg/m2 via dose escalation of 30 mg/m2) were repeated every 21 days, to a maximum of eight cycles. Maximum tolerated dose was reached if two or more of six patients at a given dose level were affected by the following events: absolute neutrophil count less than 500/microliter for > or = 7 days, absolute neutrophil count less than 100/microliter for > or = 3 days, insufficient hematopoietic recovery with absolute neutrophil count less than 1,500/microliter on day 21, febrile neutropenia, grade 4 thrombocytopenia, any World Health Organization grade 3 nonhematologic toxicity for more than 7 days. There were 19 patients enrolled; the patients received a total of 128 treatment courses. Grade 4 neutropenia was the main side effect, occurring in 20% of courses but generally not associated with clinical events. No relevant clinical cardiac toxicity or alteration of left ventricular ejection fraction was observed. Other toxicities included complete alopecia, mild peripheral neuropathy, and mild myalgia. There was a reduction of one dose level for moderate myalgia in one patient (190 mg/m2 level). Complete alopecia was always present. Maximum tolerated dose was not reached at paclitaxel 250 mg/m2. Ultimately, the introduction of this combination in the adjuvant setting is warranted.

Adult↗
PubMed1996

Activity and safety of epirubicin plus paclitaxel in advanced breast cancer.

We performed a dose-escalation study to evaluate the maximum tolerated dose (MTD) of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus a fixed dose of epirubicin. Epirubicin was administered as a 90 mg/m2 bolus immediately followed by a 3-hour infusion of paclitaxel starting at 135 mg/m2 and escalating by 20mg/m2 for each triplet of patients as long as no dose-limiting toxicity had occurred; courses were repeated every 3 weeks. The MTD was defined as that at which any of the following toxicities occurred in at least two of six patients: absolute neutrophil count less than 500/microliter for more that 7 days or less than 100/microliter for more than 3 days; any episode of febrile neutropenia requiring intravenous antibiotics and hospitalization; grade 4 thrombocytopenia requiring platelet transfusion; failure to recover absolute neutrophil count to > or = 1,500/microliter and/or platelets to > or = 100,000/microliter by day 28; and any grade > or = 3 nonhematologic toxicity. Two MTDs were defined: the first without granulocyte colony-stimulating factor (MTD 1) and the second with granulocyte colony-stimulating factor given either to accelerate recovery of grade 4 neutropenia lasting more than 72 hours or immediately in case of febrile neutropenia (MTD 2); granulocyte colony-stimulating factor was never used prophylactically. To date, 22 patients have been entered into the study; the median patient age was 55 years (age range, 30 to 66 years). Nineteen (86%) patients had received adjuvant chemotherapy that included anthracyclines in 12 cases (55%). The viscera were the dominant sites of disease in 55% of patients. Median baseline ventricular ejection fraction was 58% (range, 53% to 67%). Short-lasting grade 4 neutropenia occurred in 61% of courses; however, only four episodes of febrile neutropenia were recorded. Grade 4 thrombocytopenia was reported in 8% and grade 3 anemia in 3% of courses; four patients experienced peripheral neuropathy (three patients grade 1, one patient grade 2); complete alopecia was universal. The cardiac effects of the combination were surprisingly low: median ejection fraction at study entry was 58%, and after a cumulative dose 1,080 mg/m2 it was 56%. Three complete responses and 12 partial responses have been documented for an overall response rate of 83.3% (95% confidence interval, 58% to 96%). In conclusion, neutropenia is the most frequent toxicity of this novel combination. However, the MTD has not yet been reached. The combination of epirubicin plus paclitaxel is highly active, and no signs of cumulative myocardiopathy have been observed.

Adult↗
PubMed1996

A phase I/II study of sequential doxorubicin and paclitaxel in the treatment of advanced breast cancer.

Based on preclinical data, we designed a phase I/II clinical trial to determine the efficacy and toxicity of doxorubicin followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer (either untreated or relapsed after adjuvant therapy). In the phase I study, 19 enrolled patients received bolus doxorubicin (50 mg/m2) and, after a 16-hour interval, escalating doses of paclitaxel (from 130 to 250 mg/m2 in 30-mg/ m2 increments) by 3-hour infusion every 3 weeks for a maximum of eight cycles. Paclitaxel doses were increased if the maximum tolerated dose (MTD; defined by dose-limiting toxicities) had not been reached. Analysis of the 128 cycles assessable for toxicity demonstrated neutropenia (< 500/microL) in 20% of cycles with no significant clinical events. No relevant clinical cardiotoxicity was observed. Other toxicities included mild peripheral neuropathy and mild myalgia/arthralgia (In 37.5% and 30.4% of cycles, respectively). The maximum tolerated paclitaxel dose was not reached at the 250 mg/m2 dose level. In the second phase, 13 patients were treated with fixed doses of both drugs (doxorubicin 50 mg/m2 and paclitaxel 220 mg/m2, the dose level immediately preceding the highest paclitaxel dose used in phase I). Grade 4 neutropenia occurred in 36 of the 87 cycles but was complicated by fever in only eight cycles (9%); three patients needed granulocyte colony-stimulating factor. Peripheral neuropathy (grades 1 and 2 in 41.3% and 5.7% of cycles, respectively) and a myalgic syndrome (grades 1 and 2 in 24.1% and 17.2% of cycles, respectively) were observed. No significant clinical cardiotoxicity was observed in 12 of the 13 patients. One patient experienced a decrease in left ventricular ejection fraction (from 60% to 43%) at a cumulative doxorubicin dose of 400 mg/m2. Antitumor efficacy was evaluated in both phase I and phase II. Overall clinical responses included 10 complete (31.3%) and 15 partial (46.9%) responses, for an objective response rate of 78.1%. Six patients (18.8%) had stable disease. The median durations of objective and complete response were 9 and 7 months, respectively. The 78.9% objective response rate in the phase I trial (31.6% complete and 47.3% partial responses) suggests a dose response relationship: at paclitaxel dose > or = 190 mg/m2, all patients had an objective response (six complete and nine partial responses). These results confirm that doxorubicin followed by paclitaxel is active and should be tested as adjuvant treatment and in patients treated previously with anthracyclines.

Adult↗
PubMed1996

A dose-finding study of epirubicin in combination with paclitaxel in the treatment of advanced breast cancer.

We performed a dose escalation study to evaluate the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 3 hours plus bolus epirubicin 90 mg/m2. The starting dose of paclitaxel, 135 mg/m2, was escalated by 20-mg/m2 increments in cohorts of three to six patients. Courses were repeated every 3 weeks. Filgrastim (5 micrograms/kg/d) was administered to shorten the duration of grade 4 neutropenia lasting longer than 72 hours. Twenty-nine patients have been treated, 86% of whom had failed adjuvant chemotherapy (with anthracyclines in 14 cases). One hundred forty-eight courses have been administered, and the paclitaxel dose has been escalated to 225 mg/m2 without reaching the maximum tolerated dose. The most frequent dose-related toxicity has been grade 4 neutropenia, which occurred in 59% of courses. The median duration of grade 4 neutropenia was 4 days, which was shortened with filgrastim only in patients treated with paclitaxel 225 mg/m2. Eleven episodes of febrile neutropenia (7% of courses) have been observed. Nonhematologic toxicities were mild or moderate: grade 1 or 2 peripheral neuropathy was reported by 41% and 10% of patients, respectively. The cardiac toxicities of this regimen were surprisingly low: median left ventricular ejection fraction was 57% at study entry and 56% after six courses. Only two patients showed a decrease of left ventricular ejection fraction below 50% after six courses, and no signs of anthracycline-induced congestive heart failure were noted. The activity of this novel combination is encouraging: the overall response rate is 80%, with 16% complete responses. We have demonstrated that the combination of epirubicin plus paclitaxel given over 3 hours is feasible with acceptable toxicities, does not appear to be associated with clinically relevant cardiotoxicity, and is active in a population of patients who have failed adjuvant chemotherapy.

Adult↗
PubMed1996

Quantitative analysis of cellular proliferative activity in 35 T-cell non-Hodgkin's lymphomas. Use of proliferating cell nuclear antigen and Ki-67 (MIB-1) antibodies and nucleolar organizer regions.

OBJECTIVE: To analyze-cellular proliferation in non-Hodgkin's lymphoma (NHL) of T-cell origin using three variables available on histologic paraffin, dewaxed sections. STUDY DESIGN: The study group consisted of 35 T NHLs (22 low and 13 high grade). Two immunohistochemical methods established the percentage of cells expressing proliferating cellular nuclear antigen (PCNA), or PCNA index, and the Ki-67 antigen, or MIB-1 index. The third method quantified nucleolar organizer regions (NORs) with an image analyzer, giving the NOR area and number of NORs; an internal reference on lymphocytes was used. RESULTS: For the PCNA index, each subtype of low grade NHL demonstrated a difference as compared with high grade NHL except for angioimmunoblastic type NHL (AILD). The difference between the two grades became significant after including AILD-type NHL within high grade NHL (P = .02). The MIB-1 index gave similar results. The PCNA index and MIB-1 correlated (r = .55, P = .008). The relative NOR area and number of NORs differed significantly between the two grades (P < 10(-4) and P < 10(-2); the absolute NOR area differed to a lesser degree (P = .02), and no difference was observed for the absolute number of NORs (P = .07), stressing the importance of an internal reference. NOR areas and numbers correlated highly (r = .90 for relative and .78 for absolute variables, P < 10(-4)). No relation was found between PCNA and MIB-1 indexes. CONCLUSION: Correlations between these variables and grades of malignancy, between the two indices with each other and between the AgNOR variables with each other, including referring to internal lymphocytes, were reported for these T NHL-like tumors in studies on B NHL. The proliferative character of the AILD-type T NHL was in accordance with their worse prognosis. The absence of a correlation between PCNA or MIB-1 indices and NOR variables may reflect a biologic difference between B and T NHLs in a shorter cell cycle or more important functional activity in T NHL.

Cell Division↗
PubMed1996

The sequential administration of combined doxorubicin and paclitaxel in the treatment of advanced breast cancer.

In phase I and II studies we administered fixed doses of doxorubicin by intravenous bolus 16 hours before escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) for the treatment of patients with advanced breast cancer who had received no prior treatment or who had relapsed after adjuvant therapy. Nineteen patients were entered in the study from April 1994 to February 1995. The median age of participants was 54 years; the median disease-free interval was 328 days. Eleven patients had undergone prior adjuvant chemotherapy, seven had undergone prior hormonal therapy, and six had undergone chest radiotherapy. A total of 128 courses of fixed-dose doxorubicin 50 mg/m2 by intravenous bolus and paclitaxel (doses escalated from 130 to 250 mg/m2, through dose escalations of 30 mg/m2 if maximum tolerated dose was not reached) were repeated every 21 days for a median of seven cycles per patient. Toxicities encountered in this trial included grade 4 neutropenia (20% of courses) and grade 4 thrombocytopenia (3% of courses). No grade 3 or 4 nonhematologic toxicities were observed (World Health Organization grade I peripheral neuropathies and mild myalgias in 37.5% and 30% of courses, respectively). No cardiac toxicity was observed. Responses included six complete responses (31.6%), nine partial responses (47.2%), and three stable disease (15.8%), for an overall response rate of 78.8%. Median duration of overall and complete response was 8+ months and 7+ months, respectively. At dose levels > or = 190 mg/m2, all patients had achieved a response (six complete responses and six partial responses). A phase II trial using fixed doses of doxorubicin (50 mg/m2) and paclitaxel (220 mg/m2) is ongoing. Preliminary data on 71 courses report no cardiac toxicity. Treatment with paclitaxel has been well tolerated at each dose level. The maximum tolerated dose was not reached at 250 mg/m2. No cardiac toxicity was reported. The dosing sequence of doxorubicin followed by paclitaxel is a highly active regimen and needs to be tested in anthracycline patients and in an adjuvant setting.

Adult↗
PubMed1996

Paclitaxel combinations as front-line and salvage chemotherapy regimens in advanced breast cancer.

Thirty-two patients with advanced breast cancer have been treated with epirubicin 90 mg/m2, immediately followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infused over 3 hours, every 21 days. The starting paclitaxel dose was 135 mg/m2, increased in subsequent triplets of patients until the maximum tolerated dose was reached at 200 mg/m2. One hundred seventy-six courses have been administered; dose-related grade 4 neutropenia was observed in 66% of the courses, with 12 episodes of febrile neutropenia. Two patients showed a decline of left ventricular ejection fraction below 50% after six courses, but no signs of congestive heart failure have been reported. The response rate is 76% (95% confidence interval, 56% to 90%), with 14% complete remissions. This level of activity is encouraging considering that 84% of the patients had failed adjuvant chemotherapy (with anthracyclines in 14 cases), and 19 had progressive disease following hormone therapy for metastasis. In another study, the toxicity and activity of a salvage regimen consisting of paclitaxel 135 mg/m2 over 3 hours plus vinorelbine 25 mg/m2 in an intravenous bolus on day 1 were evaluated; vinorelbine was given again on day 8 (in 14 patients) or on day 3 (in 20 patients), and the courses were repeated every 3 weeks. Thirty-four previously treated patients with advanced breast cancer entered the study; 20 had received one prior line of chemotherapy, II had two lines, and three patients had three lines. Thirty-two patients had been exposed to anthracyclines. Grade 4 neutropenia was observed in 64% of the courses, with 13 episodes of febrile neutropenia; four episodes of grade 3 mucositis have been reported with vinorelbine days 1 and 3. A delay in the administration of chemotherapy was necessary in 17% of the courses with vinorelbine days 1 and 8 and 16% of the courses with vinorelbine days 1 and 3; moreover, the vinorelbine dose was reduced or the drug omitted on day 8 in 86% of the courses and on day 3 in 16% of the course. An objective response was achieved in 43% of the patients. In conclusion, the combination of paclitaxel plus vinorelbine is an active salvage regimen and can be administered at greater dose intensity with the day 1 and 3 schedule.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

New methodology for pancreatic scintiscanning imaging using 125I-L-3 Iodo-alpha-Methyl Tyrosine.

The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning, is mainly derived from the lack of adequate radiopharmaceuticals. With this purpose 125I-L-3 Iodo-a-Methyl Tyrosine (125I-IMT) has been studied, which has also been used for the diagnosis of different kind of brain tumors. The purpose of this work is the development of a quick and easy method for the synthesis and purification of the 125I-IMT in order to be used in a Nuclear Medicine Service. The L-alpha-Methyl Tyrosine was labeled with 125I using I-/I03 and afterwards purified by an anionic exchange resin. The labeling yield obtained was (96.0 +/- 0.5)% when the incubation time was 15 minutes. No significant statistical differences were observed when the incubation time was extended to 1 hour. Biodistribution studies in mice show that the percentage of activity concentration in pancreas is (34.24 +/- 14.03)% at 15 minutes post injection, remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the injection of the labeled product was (12.22 +/- 3.59) and it remained constant for 45 minutes more. These results show that 125I-IMT can be used as a diagnostic agent for pancreatic diseases. Since 123I was not available at the moment, this new methodology was developed with 125I.

Analysis of Variance↗