PubMed Health⌕ Search

Biomedical subjects

B Massuti

Publications and source records attributed to B Massuti.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients.

BACKGROUND: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor gamma, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. PATIENTS AND METHODS: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples. RESULTS: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, P = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival. CONCLUSION: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Pharmacogenomics and gemcitabine.

Approximately half of lung cancer patients present with metastases, and a large proportion will develop recurrent disease, with median survival to cisplatin-based chemotherapy of 11 months. No predictive factor of response to cisplatin-based chemotherapy is yet available in clinical practice. The nucleotide excision repair system plays a major role in repairing a variety of distorting lesions, notably platinum-induced DNA adducts. ERCC1 is a leading gene in repairing cisplatin DNA damage. We carried out three different studies examining individually the role of ERCC1, RRM1, and then both, mRNA expression in paraffin-embedded pretreatment bronchial biopsies from gemcitabine/cisplatin-treated advanced non-small-cell lung cancer (NSCLC) patients. Median survival was significantly prolonged in patients with low levels of ERCC1 or RRM1. BRCA1 is involved in homologous recombination repair, and we observed that low levels of BRCA1 mRNA significantly increased survival in gemcitabine/cisplatin-treated patients. Our observations lead us to recommend that tumors be regularly assessed for ERCC1 and BRCA1 mRNA expression in order to customize gemcitabine/cisplatin treatment.

Antimetabolites, Antineoplastic↗
PubMed2005

Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial.

BACKGROUND: Docetaxel is a widely accepted second-line treatment in advanced non-small-cell lung cancer (NSCLC) with a risk of myelotoxicity. This study evaluated the efficacy and toxicity profile of two docetaxel regimens in NSCLC patients who had failed first-line non-docetaxel-based chemotherapy. PATIENTS AND METHODS: A total of 259 patients from 33 Spanish centers were randomized to receive either docetaxel 75 mg/m(2) administered every 3 weeks (3W arm) or docetaxel 36 mg/m(2) given weekly (1W arm) for 6 weeks followed by 2 weeks of rest. The primary end point was 1-year survival; secondary end points were median survival, time to progression, response and toxicity. RESULTS: One-year survival was 27% in the 3W and 22% in the 1W arm. Median time to progression was also similar in the two arms. Median survival was 6.6 months in the 3W arm versus 5.4 months in the 1W arm (P = 0.075). Response rates were 9.3% in the 3W arm and 4.8% in the 1W arm. More patients in the 1W arm experienced mucositis [1W, nine patients (7.2%); 3W, two patients (1.6%); P = 0.032], while febrile neutropenia was significantly higher in the 3W arm [3W, 10 patients (7.8%); 1W, one patient (0.8%); P = 0.010]. CONCLUSIONS: Both weekly and 3-weekly docetaxel were effective and well-tolerated, with different toxicity profiles. In general, there was no indication to recommend the weekly schedule. However, the significant lower rate of febrile neutropenia observed in the weekly schedule makes it a good alternative for patients at risk of severe neutropenia.

Adult↗
PubMed2005

Phase II trial of the novel taxane BMS-184476 as second-line in non-small-cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate the tolerability and efficacy of BMS-184476, an analog of paclitaxel, in patients with advanced non-small-cell lung cancer (NSCLC) progressing or relapsing following at least one prior chemotherapy regimen. PATIENTS AND METHODS: Fifty-six previously treated advanced NSCLC patients received BMS-184476 at a dose of 60 mg/m(2) administered intravenously over 1 h every 21 days. RESULTS: The median number of cycles delivered per patient was five (range one to 17). Dose reduction was required in only 3.8% of cycles. Grade 4 neutropenia occurred in 19.6% of patients, but no grade 4 thrombocytopenia or anemia was reported. Febrile neutropenia was observed in only two (3.6%) patients and there were no life-threatening events. Grade 3/4 peripheral sensory-motor neuropathy was reported in 9% of patients. Other non-hematological toxicities, such as nausea and vomiting, myalgia and arthralgia, diarrhea, and mucositis, were uncommon. Partial responses were observed in eight (14.3%) patients and stable disease in 33 (58.9%). Median progression-free survival was 3.7 months [95% confidence interval (CI) 2.7-5.4] and median overall survival was 10 months (95% CI 6-13.4). CONCLUSIONS: BMS-184476 was well tolerated at the dose of 60 mg/m(2) and showed evidence of antitumor activity in previously treated NSCLC.

Adult↗
PubMed2003

Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group.

BACKGROUND: The purpose of this study was to determine the relative efficacy of doxorubicin versus methotrexate in combination with intravenous cyclophosphamide and 5-fluorouracil (FAC versus CMF) as adjuvant chemotherapy for operable breast cancer. PATIENTS AND METHODS: Over a 4-year period, 985 women undergoing curative surgery for breast cancer (T1-3 N0-2 M0, stage I-IIIA, UICC) from nine hospitals were stratified with respect to axillary node involvement (node positive versus node negative) and randomized to receive either FAC (500/50/500/m(2)) every 3 weeks for six cycles or CMF (600/60/600/m(2)) every 3 weeks for six cycles. RESULTS: The relative dose intensities of FAC and CMF were 87% and 85% of planned doses, respectively. Unadjusted data indicated a non-significant trend towards better results with FAC. In the prospectively formed subset of node-negative patients, disease-free survival and overall survival were statistically superior in the FAC treatment arm (P = 0.041 and 0.034, respectively), but this advantage was not seen in the subset of node-positive patients, probably because of a difference in the percentage of patients with four or more positive nodes. Adjusting data for size of treatment effect and potential interactions (number of positive nodes, tumor size, treatment center), the overall relative risk (RR) of disease recurrence and death were significantly lower with FAC treatment (RR 1.2, P = 0.03, and RR 1.3, P = 0.05, respectively). This result was mainly due to the difference observed in the node-negative patient population. Toxicity was mild: FAC induced more alopecia, emesis, mucositis and cardiotoxicity; this last was of clinical concern, but was infrequent and manageable. CMF induced more conjunctivitis and weight gain. There were no toxic deaths. CONCLUSIONS: Doxorubicin in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil is superior to methotrexate in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil as adjuvant chemotherapy for operable breast cancer. A treatment effect is particularly evident in the node-negative patients. Although the clinical toxicity of FAC is greater than that of CMF, the levels were manageable and clinically acceptable.

Adolescent↗
PubMed2000

Doxorubicin and paclitaxel in advanced breast carcinoma: importance of prior adjuvant anthracycline therapy.

BACKGROUND: The authors undertook a Phase II multicenter trial to assess the efficacy and toxicity of doxorubicin and paclitaxel in combination in the treatment of patients with metastatic breast carcinoma. METHODS: Doxorubicin (50 mg/m2, bolus) followed by paclitaxel (175 mg/m2 over 3 hours) was administered every 21 days (for a maximum of 10 cycles) as first-line chemotherapy in 77 patients, 41 of whom had received prior adjuvant chemotherapy. Monitoring of cardiac function (left ventricular ejection fraction[LVEF]) and total doxorubicin cumulative dose were included in the study protocol. RESULTS: Grade 4 hematologic toxicities were neutropenia (58%) and thrombocytopenia (4%). Neutropenic fever occurred in 9% of patients. Nonhematologic Grade 4 toxicity was limited to mucositis (3%). Grade 3 toxicities were neutropenia (35%), anemia (3%), alopecia (93%), peripheral neuropathy (18%), arthralgia/myalgia (8%), and mucositis (9%). No clinical cardiotoxicity (Grades 3 or 4) occurred. Treatment was discontinued in 5 patients who showed a decrease of LVEF of greater than 15% during therapy. Of 73 patients assessable for response, 15 were complete response, 42 partial response, 15 stable disease, and 1 disease progression; overall response rate being 78% (95% confidence interval [CI], 67-87). Median follow-up was 22 months. Median time to progression (TP) was 10 months (95% CI, 7-12). Time to progression was poorer in cases with adjuvant anthracycline therapy than those without adjuvant chemotherapy (7 vs. 12.3 months; P = 0.022), but TP in patients with adjuvant chemotherapy not containing anthracyclines was not different from the cases without adjuvant chemotherapy (8.6 months). Estimated 2-year survival was 51% (standard error, 7%). CONCLUSIONS: Our results confirm that the combination of paclitaxel and doxorubicin is effective in the treatment of metastatic breast carcinoma, and that it is well tolerated. No clinical cardiotoxicity was observed on close cardiac monitoring, and prior adjuvant anthracycline treatment compromised its efficacy.

Adult↗
PubMed2000

Economic evaluation in a randomized phase III clinical trial comparing gemcitabine/cisplatin and etoposide/cisplatin in non-small cell lung cancer.

INTRODUCTION: Information on the relative cost-effectiveness of treatments for cancer is being increasingly sought as pressure on health care resources increases. The objective of this study was to assess the cost-effectiveness of gemcitabine/cisplatin (GC) versus cisplatin/etoposide (CE) in patients with advanced non-small cell lung cancer (NSCLC), using resource utilization data collected in conjunction with the first randomized clinical trial comparing both combinations. METHODS: Efficacy and medical care resource utilization data were collected prospectively in an open-label, multicenter, randomized, comparative, phase III trial conducted in Spain which compared gemcitabine/cisplatin and cisplatin/etoposide in 135 chemonaive patients with Stage IIIB or IV NSCLC. There were no differences between both regimens when survival was used as primary end-point, so a cost-minimization analysis was used to compare them. In addition, cost-effectiveness analyses were conducted when percentage of responses and time to progression were used as secondary end-points. RESULTS: There were no differences between both regimens when survival was selected as the efficacy end-point. Despite the higher chemotherapy cost of GC when compared to CE, there were no differences in total direct costs (584523 pts for GC and 589630 pts for CE; P=NS) between both regimens. Potential savings with GC were mainly associated with a decrease in hospitalization rate. There were differences in favor of GC when response rate (40.6% for GC and 21.9% for CE; P<0.05) and time to disease progression (8.7 months for GC and 7.2 months for CE; P<0. 05) were used as clinical end-points. GC presented a favorable cost-effectiveness profile when compared to CE. CONCLUSIONS: This prospective economic evaluation conducted alongside a clinical trial offers valuable preliminary information on the potential efficiency of the combination gemcitabine-cisplatin in NSCLC. Future assessments based on larger clinical trials focused on survival and naturalistic economic studies conducted in real clinical practice settings are necessary to confirm these findings.

Aged↗
PubMed1999

Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation.

The main aim of the present study was to assess the early diagnostic value of bronchoalveolar lavage (BAL) in radiation-induced lung injury in patients with breast carcinoma. Twenty-six females receiving postoperative radiotherapy for breast cancer were evaluated before and 0, 15, 30, 60, and 180 days after radiotherapy. History, physical examination, chest radiographs, and pulmonary function tests were obtained. BAL, including lymphocyte subsets analysis, was limited to the second evaluation after radiotherapy. A group of 21 healthy females were used as control. Findings after radiotherapy in asymptomatic patients were compared with findings in a group of patients with radiation pneumonitis. Irradiated patients showed a significantly (p<0.01) greater percentage (29.5+/-15.7%) of BAL lymphocytes than controls (6.2+/-3.3%). No statistical differences existed in BAL findings between the irradiated and unirradiated sides of the chest. Percentages of BAL lymphocytes did not differ significantly between patients who developed subsequent pneumonitis (24.5+/-13.5%) and those who did not develop pneumonitis (32.8+/-16.5%). Patients with pneumonitis at the time of BAL had significantly higher (p<0.05) alveolar CD4 subset cells (24.8+/-10.2%) than asymptomatic patients (15.2+/-8.9%). Maximal reductions in total lung capacity (p<0.01), and residual volume (p<0.05) occurred 60 days after irradiation. The early lymphocytic alveolitis induced by unilateral thoracic radiotherapy in most patients with breast cancer is always bilateral and does not predict the subsequent development of radiological evidence of pneumonitis.

Breast Neoplasms↗
PubMed1999

A randomized phase II trial of 5-fluorouracil, with or without human interferon-beta, for advanced colorectal cancer.

This study compared the efficacy and safety of 5-fluorouracil (5-FU) monotherapy to that of 5-FU combined with natural human interferon-beta (IFN-beta) in patients with unresectable, advanced colorectal carcinoma. Forty-nine chemotherapy-naive patients were randomized to 5-FU alone or to the combination. All patients received 750 mg m(-2) day(-1) 5-FU for 5 days by continuous intravenous (i.v.) infusion, followed after day 15 by a weekly i.v. bolus of 750 mg m(-2). IFN-beta was injected intramuscularly three times weekly at 9 M IU. Treatment continued for 52 weeks, or until disease progression or intolerable toxicity. Clinical endpoints were tumor response, time to progression, survival and toxicity. The addition of IFN-3 to 5-FU significantly improved response rate (33.3% vs 4.5% for evaluable patients; P = 0.021), time to progression (median 7.2 vs 4.2 months; P = 0.0435), and survival time (median 15.9 vs 7.2 months; P = 0.038) without significantly increasing toxicity compared to 5-FU alone. Cumulative 5-FU dose was higher with combined therapy (P < 0.001): more patients receiving monotherapy discontinued treatment because of disease progression. Fever was more frequent with combined therapy (P = 0.008); there were no other differences in toxicity. The only grade IV toxicity observed was neutropenia (two patients per group). A randomized phase III trial has been initiated to confirm the synergy between 5-FU and IFN-beta.

Aged↗
PubMed1999

Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

Adult↗
PubMed1998

Seventy-two hour epirubicin infusion plus quinidine in unresectable and metastatic adenocarcinoma of the pancreas: a phase II trial.

Twenty-two previously untreated patients who had unresectable and metastatic pancreatic cancer were treated in a prospective phase II trial with high-dose continuous infusion epirubicin (45 mg/m2 once every 24 hours continuous infusion days 4 through 6) plus quinidine (495 mg once every 24 hours on days 1-6). There were no objective responses (0 of 18 evaluable patients). Subjective responses were achieved in 2 of 21 evaluable patients (9%), all of whom had good performance status (Eastern Cooperative Oncology Group: 0-1). Median survival was 5.7 months for the overall population. Two patients who exhibited symptomatic improvement achieved responses lasting 7 and 13 months, respectively. Toxicity was generally mild and tolerable. Little benefit regarding survival and quality of life was observed with the use of this regimen. The role in chemoresistance of mdrl, p53, and the mismatch repair system was examined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Superiority of sequential versus concurrent administration of paclitaxel with etoposide in advanced non-small cell lung cancer: comparison of two Phase II trials.

Paclitaxel and etoposide are two chemotherapy agents with broad cytotoxic activity and different mechanisms of action and resistance. Preclinical studies of their combined cytotoxicity have yielded conflicting results. We performed two sequential Phase II trials using different sequence schedules of paclitaxel and etoposide as first-line treatment in advanced non-small cell lung cancer (NSCLC). Forty-four patients with stage IIIB or IV NSCLC were included between July 1995 and September 1996. All patients received etoposide at 100 mg/m2, given as an i.v. infusion on days 1, 2, and 3. The first 20 patients (part A) also received paclitaxel at 175 mg/m2 as a 3-h infusion on day 1, immediately prior to etoposide. The subsequent 24 patients (part B) were given the same paclitaxel dose, but on day 4. Grade 3-4 granulocytopenia was seen in 70% of the patients in part A and in 37% of those in part B (P = 0.04). Twenty-five % of the courses in part A and 4% of the courses in part B were associated with granulocyte nadir < or =500/microl (P = 0.00006). No responses were observed in part A, although disease was stabilized in 14 patients (70%). In part B, there were two complete responses and seven partial responses, for an overall response rate of 37.5% (95% confidence interval, 21-58%). In conclusion, toxicity and antitumor activity of the paclitaxel/etoposide combination may be sequence dependent. Our findings suggest that etoposide followed by paclitaxel is well tolerated and has greater activity in NSCLC than concurrent administration.

Adult↗
PubMed1997

A sequence-dependent paclitaxel/etoposide phase II trial in patients with non-small cell lung cancer.

Studies conducted by the Spanish Lung Cancer Group indicate that cisplatin- or carboplatin-based chemotherapy can yield a 25% response rate, 9-month median survival time, and 30% 1-year survival rate in patients with stage III and IV non-small cell lung cancer. Phase II trials of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have an almost 30% response rate in non-small cell lung cancer. Based on these results, we decided to examine whether the sequence-dependent effects of paclitaxel/etoposide influence treatment outcome (antitumor response) and toxicity. In vitro data show a paradoxical antagonist rather than additive effect. In the first part of our study (part A), paclitaxel and etoposide were administered at the same time. In the second part (part B), etoposide preceded paclitaxel. In both parts, patients with previously untreated stage IIIB or IV non-small cell lung cancer with good performance status were eligible. In part A, etoposide (fixed dose, 100 mg/m2) on days 1, 2, and 3 was administered by 30-minute infusion; paclitaxel (175 mg/m2) was given by a 3-hour infusion on day 1. In part B, the etoposide dose and schedule were the same, but paclitaxel (same dose) was administered on day 4. Treatment in both parts was repeated every 21 days for a maximum of 10 cycles. In part A, 18 patients were entered and no objective responses were observed. In part B, 21 patients were accrued, 17 of whom had sufficient follow-up for response assessment. Seven objective responses were achieved (two complete and five partial responses, for an objective response rate of 41%). Seven patients had no change and three had progressive disease. Frequency and severity of side effects were not significantly different in either part of the study. However, grade 4 neutropenia was observed in 10 (59%) patients and one (5%) patient in parts A and B of the trial, respectively. Nonhematologic toxicity was slight. In conclusion, paclitaxel cytotoxicity is abrogated when it is given concurrently with etoposide. When etoposide precedes paclitaxel, a more effective paclitaxel/etoposide schedule is attained.

Adult↗
PubMed1997

Dose-escalated paclitaxel in 1-hour infusion with a fixed dose of cisplatin in previously untreated advanced ovarian cancer: a phase II trial of the Spanish Group for Ovarian Cancer.

This phase II trial was planned to study the efficacy and toxicity of a fixed dose of cisplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 1 hour with intrapatient dose escalation. Patients with advanced epithelial ovarian cancer (stages IIB-IV); Eastern Cooperative Oncology Group performance status < or = 2; normal renal, liver, and bone marrow function; and evaluable residual disease after debulking surgery were accrued. Paclitaxel was given over 1-hour infusion and dose was escalated from 175 to 200 and 225 mg/m2 if nadir neutrophil counts were > or = 1000/microL, platelets were > or = 100,000/microL, and neurotoxicity was less than grade 2. Cisplatin was given after paclitaxel at a fixed dose of 80 mg/m2. Six courses at 3-week intervals were planned. From May 1995 to August 1996, 68 patients were entered. Paclitaxel could not be escalated in six patients, another six received up to 200 mg/m2, and 45 received 225 mg/m2. Three hundred seventy-five courses were given: 27.7% at 175 mg/m2, 19.2% at 200 mg/m2, and 53.1% at 225 mg/m2. All patients were evaluable for toxicity, and 67 were evaluable for response. Thirty-five patients had a complete clinical response (51.4%), 20 had a partial response (29.4%), six had stable disease (8.9%), and six progressed on therapy (8.9%). Overall response rate was 80.8 (95% confidence interval, 71.3% to 90.1%). Second-look laparotomy was performed in 32 patients, and 20 of them (62.5%) had a pathologic complete remission. Grade 3 or 4 neutropenia was seen in 26 patients (38%), but only one had fever. Severe thrombocytopenia was not seen. Peripheral neurotoxicity (grade 1, 39.7%; grade 2, 42.6%; and grade 3, 8.8%) was dose-limiting. It is too early to report on time to progression and survival, and these data are not yet available. This combination of cisplatin with escalating doses of paclitaxel is feasible and very active, but the high incidence of peripheral neurotoxicity may limit its use.

Antineoplastic Agents↗
PubMed1997

Paclitaxel plus doxorubicin in metastatic breast cancer: preliminary analysis of cardiotoxicity.

This ongoing phase II trial was designed to determine the antitumor activity and cardiotoxicity of a combination of doxorubicin (50 mg/m2) and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 to 225 mg/m2 over 3 hours) as first-line chemotherapy for metastatic breast cancer. Of 76 patients entered so far, 57 who had received at least three courses of chemotherapy are assessable for efficacy and cardiac toxicity. A slight majority (57%) of the patients entered had prior adjuvant chemotherapy, including 33% with anthracycline-containing combinations. An objective response was achieved by 70% of patients, with 18% complete responders. The main noncardiac toxicities were alopecia, neutropenia, mucositis, and peripheral neuropathy. Overall, after a median cumulative doxorubicin dose of 350 mg/m2, the evolution of left ventricular ejection fraction (LVEF) values did not significantly decrease from baseline to the sixth course of therapy. However, LVEF values decreased significantly in eight patients (14%). The LVEF decreased by more than 14% over basal values in three patients, although the final determination was still above the lower limits of normal. The remaining five patients had LVEF decreases that fell below the lower limits of normal (33% to 48%). None of the patients developed clinically evident heart failure. Our results indicate that the combination of doxorubicin (50 mg/m2) plus paclitaxel (175 to 225 mg/m2) is effective and does not induce a clinically relevant cardiotoxicity.

Adolescent↗
PubMed1992

Etoposide (E) + epirubicin (E) + cisplatin (P) combination chemotherapy (EEP) in advanced gastric cancer: negative impact on clinical outcome. Spanish Cooperative Group for GI Tumor Therapy (T.T.D.).

One hundred nineteen patients with advanced gastric cancer were included in a study comparing EEP vs. FEM chemotherapy. The response rate was higher (30%) in patients on EEP than in those treated with FEM (p = 0.05). Severe leukopenia, anemia, alopecia and infection were significantly more frequent on EEP. In addition, because of its intrinsic toxicity, EEP chemotherapy has a negative impact on the performance status of patients treated with this regimen, more than half of whom presented at least one episode of severe symptomatic toxicity while on EEP chemotherapy. The median time to progression and median survival for EEP-FEM were 2.08-3.4 and 4.2-7.9 months, respectively. Our data do not support the use of EEP chemotherapy in patients with AGC.

Antineoplastic Combined Chemotherapy Protocols↗