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Biomedical subjects

L Zelek

Publications and source records attributed to L Zelek.

At least 19 recordsLinked to original sources
PubMed2006

A phase II study of Yondelis (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer.

Yondelis (trabectedin, ET-743) is a novel marine-derived anticancer compound found in the ascidian Ecteinascidia turbinata. It is currently under phase II/III development in breast cancer, hormone refractory prostate cancer, sarcomas and ovarian cancer. Activity in breast cancer experimental models has been reported, and preliminary evidence of activity in this setting during the phase I programme has also been observed. The present study assessed the activity and feasibility of trabectedin in women with advanced breast cancer previously treated with conventional therapies. Patients with advanced disease previously treated with at least one but not more than two regimens that included taxanes or anthracyclines as palliative therapy were eligible. Trabectedin 1.5 mg m(-2) was administered as a 24-h continuous infusion every 3 weeks. Patients were kept on therapy until disease progression, unacceptable toxicity or patient refusal. Twenty-seven patients were included between April 1999 and September 2000. Their median age was 54 years (range: 36-67) and 63% of them had two metastatic sites. Twenty-two patients were performance status 1. All patients had previously received anthracyclines, and 23 out of 27 patients had received taxanes. Of 21 patients with measurable disease, three confirmed partial responses, one unconfirmed partial response and two minor responses (49 and 32% tumour shrinkage) were observed; six patients had stable disease. Median survival was 10 months (95% confidence interval: 4.88-15.18). Transient and noncumulative transaminitis was observed in most of the patients. The pharmacokinetic profile of trabectedin in this patient's population is in line with the overall data available with this schedule. The policy of dose adjustments based on the intercycle peaks of bilirubin and alkaline phosphatase appears to have a positive impact in the therapeutic index of trabectedin. Trabectedin can induce response and tumour control in previously treated advanced breast cancer, with manageable toxicity, thus warranting further development as a single agent or in combination regimens.

Adult↗
PubMed2005

[Chemotherapy in soft tissue sarcomas].

Despite they represent an heterogeneous entity, the same protocols were applied to all subtypes of soft-tissue sarcomas until recently. Although doxorubicin and ifosfamide remain the cornerstone of therapy, their association yields enhanced response rates but has no obvious effect on survival. The benefit of adjuvant therapy is still matter of debate; however, it seems to improve relapse-free survival and might of particular interest for patients with high-grade tumours of the extremities. Yet, the major change occurring over the past few years is probably the development of subtype-specific regimens. Whether targeted therapies could provide additional benefit is a major concern but further studies are needed.

Humans↗
PubMed2005

Dealing with metastatic breast cancer in elderly women: results from a French study on a large cohort carried out by the 'Observatory on Elderly Patients'.

BACKGROUND: Treatment of elderly patients with metastatic breast cancer (MBC) is not clearly defined and seems to vary according to the subjective appreciation of the physician. PATIENTS AND METHODS: After interviewing 107 French specialists qualified in oncology, data concerning 1009 MBC patients were collected: 500 patients were between 65 and 74 years and 509 were >75 years of age. Differences in diagnosis and treatment strategy were analyzed for both age groups to identify the physician's criteria of choice and the eventual use of the geriatric assessment among those criteria. RESULTS: At diagnosis, synchronous metastatic disease was more frequent in patients over 75 years old (52% versus 39%; P<0.001). Physicians indicated that treatment was based on age and on a subjective evaluation of the patient's general status. Sixty-eight per cent of younger patients and only 31% of older ones received chemotherapy (P<0.001). In the older group drug doses were lower than those usually recommended in three-quarters of cases. Only 10% of physicians considered that they under-treat patients using the FEC 50 regimen. Over 75 years of age, hormone therapy was offered to most patients, including 8% with hormone-independent tumors. Geriatric covariates were never considered. Geriatricians rarely, if ever, played a role in the therapeutic decision. CONCLUSIONS: Inclusion of elderly patients with MBC in prospective trials is warranted to define standards of care and reduce heterogeneity in the decision-making process.

Age Factors↗
PubMed2004

Efficacy and safety of single agent capecitabine in pretreated metastatic breast cancer patients from the French compassionate use program.

BACKGROUND: A retrospective source review identifying predictive factors and assessing safety and efficacy in pretreated metastatic breast cancer (MBC) patients treated with capecitabine in a French compassionate-use program. PATIENTS AND METHODS: 197 patients received capecitabine at an initial total dose 0.25-3.0 g/m2/day, twice daily for 14 consecutive days, every 3 weeks. RESULTS: Median patient age was 56 years (range, 31-88), 19% had performance status (PS) 3-4. Prior palliative and adjuvant treatment was reported in 96 and 61% of patients respectively. Best overall response rate (ORR) was 15% (95% confidence interval [CI], 11-21%) and 49% had benefit (CR, PR or SD). Median time to progression (TTP) and overall survival were 4.8 and 14.7 months, respectively. Median TTP in responders was 8.9 months (95%CI 6.1-11.7). Grade 3/4 neutropenia and grade 3 thrombocytopenia occurred in 8 and 3% of patients respectively. Hand-foot syndrome (grade 3/4 in 16% of patients), diarrhea, stomatitis and asthenia were prevalent. Multivariate analysis showed ORR was significantly influenced by PS > or = 2 (p = 0.004), time from metastases diagnosis to capecitabine treatment (p = 0.015) and presence of liver metastases at inclusion (p = 0.047). Abnormal liver function tests at baseline were associated with severe thrombocytopenia and anemia. Four treatment-related deaths occurred. CONCLUSION: Capecitabine is active in heavily pretreated MBC patients and has a favorable toxicity profile with the added advantage of being an oral drug administered in an outpatient setting.

Administration, Oral↗
PubMed2003

Prognostic factors in primary breast sarcomas: a series of patients with long-term follow-up.

PURPOSE: To describe the pathologic characteristics and prognostic factors of primary breast sarcomas (PBSs). PATIENTS AND METHODS: We reviewed the clinical records and pathologic slides of 83 women with PBS treated in our institution between 1954 and 1991, with a median follow-up of 7.8 years. The majority of patients had undergone surgical treatment. RESULTS: The main histologic type was malignant fibrohistiocytoma (n = 57). For the whole population, the 10-year overall survival (OS) and disease-free survival (DFS) rates were 62% and 50%, respectively. For Fédération Nationale des Centres de Lutte Contre le Cancer grade 1, 2, and 3 tumors, the 10-year OS and DFS rates were 82% and 61%, 62% and 51%, and 36% and 25%, respectively (P =.00007 and.004, respectively). For tumors measuring less than 5 cm, 5 to 10 cm, and more than 10 cm, the 10-year OS and DFS rates were 76% and 66%, 68% and 55%, and 28% and 15%, respectively (P =.002 and.009, respectively). In the multivariate analysis, the tumor size and histologic grade were correlated with the 10-year DFS rate (P =.04 and.01, respectively), but only the histologic grade was correlated with OS (P =.01). Angiosarcoma was the only histologic type significantly associated with a poorer outcome in the multivariate analysis. CONCLUSION: PBSs have the same clinical history and prognostic factors as sarcomas arising at other sites. Therefore, it is legitimate to use a similar treatment strategy for PBS as for other sarcomas.

Adolescent↗
PubMed2003

Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines.

BACKGROUND: To assess antitumor activity and toxicity of pemetrexed in metastatic breast cancer (MBC) patients previously treated with anthracyclines. PATIENTS AND METHODS: Seventy-seven MBC patients from 12 European institutions were entered into the study. Seventy-two patients were considered evaluable for response and toxicity. Forty-two patients were classified as anthracycline-failure (relapse >30 days after completion of a prior anthracycline regimen) and 30 as anthracycline-refractory (progression within 30 days after anthracycline therapy). Pemetrexed 600 mg/m(2) was administered intravenously every 3 weeks until progressive disease or unacceptable toxicity. RESULTS: There were three complete and 12 partial responders [response rate 21% (95% confidence interval 12%)]. Response rates in the anthracycline-failure and anthracycline-refractory groups were 24% and 17%, respectively. A subset of 31 patients pretreated with anthracyclines and taxanes had a response rate of 26%. Median duration of response and median survival were 5.5 and 10.7 months, respectively (13 months in the failure group and 5.7 months for refractory). Grade 3/4 toxicities included neutropenia and thrombocytopenia in 56% and 19% of patients, respectively. Nine patients (12%) experienced neutropenic fever. Grade 3/4 non-hematological toxicities included skin rash (10%), nausea (12%), fatigue (10%) and stomatitis (5%). CONCLUSION: Our trial demonstrates pemetrexed to be active in breast cancer, with manageable toxicity. Activity of pemetrexed did not appear to be adversely affected by prior taxane, 5-fluorouracil or endocrine treatments.

Adult↗
PubMed2003

Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial).

BACKGROUND: The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter. RESULTS: The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months. CONCLUSION: The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.

Adult↗
PubMed2002

Phase II study of oxaliplatin and fluorouracil in taxane- and anthracycline-pretreated breast cancer patients.

PURPOSE: Phase II study evaluating efficacy and safety of combined oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic breast cancer (ABC) patients. PATIENTS AND METHODS: Sixty-four taxane- and anthracycline-pretreated (within 6 months of study entry) women were treated with oxaliplatin 130 mg/m(2) (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m(2)/d (continuous IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median patient age was 51 years (range, 34 to 71 years), with a median of two involved organs (range, one to six organs), and metastases in the liver (70%), bone (47%), and lung (34%). Patients had a median of two prior chemotherapy regimens (range, one to six regimens), and 78% had previous hormonal therapy, with clinical taxane and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles were administered, with a median of six cycles/patient (range, one to 15 cycles). Sixty patients were assessable for response (World Health Organization criteria): 17 partial response, 26 stable disease, and 17 disease progression, giving an overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26% and 36% in taxane- and anthracycline-resistant populations, respectively, all responders having metastatic liver disease. Median time to progression was 4.8 months, and median overall survival was 11.9 months. Four treatment-related serious adverse events occurred, seven patients withdrew because of treatment-related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4 neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients, respectively, and a single episode of febrile neutropenia. One third of patients developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with grade 3 in only 8%. CONCLUSION: This oxaliplatin/5-FU combination is effective with an excellent safety profile in anthracycline/taxane-pretreated ABC patients, showing encouraging activity in patients with anthracycline/taxane-resistance or visceral disease.

Adult↗
PubMed2001

Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma.

BACKGROUND: Currently, there is no gold standard for the treatment of patients with metastatic breast carcinoma who have experienced failure with anthracyclines and taxanes. A biologic rationale suggests that the mechanism of taxane resistance could be because of an excess of depolymerized tubulin that could enhance sensitivity to vinorelbine. The objective of the study was to assess the tolerance and efficiency of weekly vinorelbine in metastatic breast carcinoma after failure with taxanes. METHODS: Patients with measurable disease, a World Health Organization performance status of less than 3 and a life expectancy longer than 3 months were eligible. Persistent taxane-induced neuropathy higher than Grade 1 was an exclusion criterion. The initial planned dose was 30 mg/m(2)/week on an outpatient basis without granulocyte colony-stimulating factor (G-CSF). Neutrophil and platelet counts of 1.0 and 80 g/L, respectively, were required before each new injection; otherwise vinorelbine was delayed for 7 days with a dose reduction of 5 mg/m(2) at the second episode. The dose also was reduced if Grade 3 or 4 toxicity occurred. If the adverse event persisted or if the delay exceeded 14 days between 2 injections given at a dose of 20 mg/m(2), vinorelbine was definitively discontinued. RESULTS: Between November 1997 and March 1999, 40 patients with a median age of 49 (range, 39-69) were enrolled. All of them had previously received anthracyclines and taxanes. Because of the delays in neutrophil recovery, the median dose intensity did not exceed 22.5 mg/m(2)/week (range, 11.25-30), and the initial planned dose of 30 mg/m(2)/week appeared unfeasible without G-CSF. The starting dose therefore was 25 mg/m(2)/week after the first 6 patients. Neutropenia led to fever in only three patients. Other severe toxicities were Grade 2-3 neuropathy (n = 5), Grade 2-3 ileus (n = 7), Grade 3 anemia (n = 4), and Grade 3 sepsis (n = 1). Objective responses were observed in 10 of 40 patients (25%), 7 of whom had visceral metastases and 4 who were refractory to taxanes (including 2 patients with liver involvement > 50%). The median time to failure was 6 months (range, 4-12) for responding patients. Disease stabilization was achieved in 9 patients (23%) for a median duration of 5 months (range, 4-6). The median survival duration for the whole population was 6 months (range, 2-18+). CONCLUSIONS: Weekly vinorelbine is an active salvage therapy for metastatic breast carcinoma after failure with anthracyclines and taxanes, even in patients with taxane-refractory metastatic breast carcinoma. This confirms that vinorelbine and taxanes are not cross-resistant.

Adult↗
PubMed2001

Metachronous gonadal and extragonadal primaries, or late relapse of germ cell tumor?

We report five distinct cases of apparently metachronous extragonadal and gonadal germ cell tumors (GCT) occurring in the same patient. Two patients had metachronous GCT of the central nervous system and the testis. One of these patients had been successfully treated for a germinoma of the pineal gland and developed a nonseminomatous GCT of the testis 10 years later. The second patient had a primary seminoma of the testis treated by orchiectomy followed by radiotherapy and developed a germinoma of the sphenoidal sinus 17 months later. Three other patients had an apparently metachronous retroperitoneal and testicular GCT with 22, 44, and 66 months elapsing, respectively, between the first and second neoplasms. These cases suggest that the remaining testis is not only at risk for a second primary GCT, but that a second GCT may emerge at an extragonadal site. A genetic predisposition may account for some of these cases and the occurrence of bilateral testicular GCT. In none of these cases, however, could we ascertain whether testicular GCT was truly a second primary or a relapse of a "primary" retroperitoneal GCT in our cases.

Journal Article↗
PubMed2001

Single-agent estramustine phosphate (EMP) is active in advanced breast cancer after failure with anthracyclines and taxanes.

PURPOSE: Estramustine phosphate (EMP) is an oral cytotoxic agent that depolymerizes tubuline, a mechanism of action that has been revisited during the last decade. Because of its lack of haematological toxicity and favourable tolerance profile, EMP is a good candidate for palliative chemotherapy. The aim of the study was to assess its tolerance and efficacy in advanced breast cancer after failure with usual regimens. PATIENTS AND METHODS: Patients with a life expectancy of at least 12 weeks and bi-dimensionally measurable disease having received at least 1 line of chemotherapy (including taxanes and/or anthracyclines) for advanced breast cancer (ABC) were eligible. EMP was given daily at a dose of 10 mg/kg until disease progression, unacceptable toxicity or patient refusal to continue chemotherapy. RESULTS: Forty patients were included between June 1998 and December 1999. Patients had previously received one to eight chemotherapy regimens (median is two) for ABC. Twenty-two patients (55%) had visceral involvement and eighteen patients (45%) had osseous, chest wall or soft tissue metastases. Adverse events leading to early interruption of EMP were grade 2 allergy (n = 1), grade 2-3 nausea (n = 6), deep-vein thrombosis (n = 1), grade 3 sepsis (n = 1). One patient died at twenty-four weeks from pulmonary embolism, and another at fourteen weeks from unknown cause. Seven objective responses were observed (17.5%; 95% confidence interval (CI): 6%-30%). Median time to failure was 24 weeks (14-52+) in responding patients. All objective responses but one were observed in patients with visceral metastases. In 10 other patients (25%), disease remained stable with a median time to failure of 27 weeks (16-50); 6 of these experienced a decrease of consumption of analgesics or an improvement of performance status. CONCLUSION: EMP is an active drug in ABC after failure with taxanes and anthracyclines, whose tolerance profile appears favourable.

Administration, Oral↗
PubMed2001

A before-after study using OncoDoc, a guideline-based decision support-system on breast cancer management: impact upon physician prescribing behaviour.

Guideline-based decision support systems have been developed to influence the prescribing behaviour of clinicians, but they have not yet shown to increase physician compliance with best practices in routine. OncoDoc is a non-automated system that allows flexibility in guideline interpretation to obtain best patient-specific recommendations at the point of care. OncoDoc is applied to breast cancer management. We have experimented the system at the Institut Gustave Roussy with a before-after study in which treatment decisions for breast cancer patients were measured before and after using the system in order to evaluate its impact upon physicians' prescribing behaviour. After 4 months, 127 decisions were recorded. Physicians compliance with OncoDoc was significantly improved (p < 10(-4) ) to reach 85.03% after using the system. Comparison of initial and final decisions showed that physicians modified their prescription in 31% of the cases. Clinical trial accrual rate increased of 50%, though not statistically significant because estimated on small figures.

Artificial Intelligence↗
PubMed2000

Loss of heterozygosity, allele silencing and decreased expression of p73 gene in breast cancers: prevalence of alterations in inflammatory breast cancers.

The p73 gene is a p53 homologue located at 1p36-33, a region submitted to deletions in breast cancer (BC) and putatively imprinted. To study whether p73 was associated with breast carcinogenesis, loss of heterozygosity (LOH), allele expression and transcript levels were assessed in 59 BC, including 39 BC presenting no inflammatory symptoms (NBC) and 20 inflammatory BC (IBC). IBC is a rare but aggressive form of cancer with a very poor prognosis. Normal breast epithelium (BE) and lymphocytes from patients were used as controls. StyI polymorphism generating GC and/or AT alleles was used to select 22 heterozygous patients. p73 LOH was significantly higher in IBC than in NBC [five of eight cases (62%) versus two of 14 cases (14%); Fisher's exact test, P=0.05]. p73 was biallelically expressed in all BE. In contrast, 12 of 16 (75%) BC were monoallelically expressed, showing that allele silencing was significantly associated with breast carcinogenesis (P=0.012), AT being the preferential silent allele (10 out of 12 tumours). p73 mRNA levels in NBC and IBC were two- and threefold lower than in BE, respectively, suggesting that decreased expression could be related to tumour aggressiveness. In conclusion, LOH, allele silencing and decreased expression of the p73 gene may play a role in breast carcinogenesis.

Alleles↗
PubMed2000

Is òne cycle every three or four weeks' obsolete? A critical review of dose-dense chemotherapy in solid neoplasms.

BACKGROUND: Shortening the interval between cycles is one means of increasing the dose intensity of chemotherapy, and can be supported by biological and mathematical rationales. Our objective was to assess the clinical relevance of the rapid repetition of regimens (so-called 'dose-dense chemotherapy') in various solid neoplasms. DESIGN: The medical literature was reviewed in accord with Mulrow's recommendations. Randomised studies comparing frequently-repeated chemotherapy to standard regimens as well as open studies are described and critically examined. RESULTS: Dose-dense regimens were widely found to be feasible. In small-cell lung cancer, survival of patients receiving dose-dense regimens was better than that of patients treated by standard chemotherapy in three trials, two of which reached significance, when these intensive regimens allowed better dose intensity. In poor-prognosis germ-cell tumors, a dose-dense regimen was not better than standard therapy, perhaps because of an excessively high toxicity-related death rate. However, recent phase II studies have provided encouraging results. In early breast cancer, the one published randomized study in the adjuvant setting showed only a trend towards better disease-free survival in node-positive women receiving a weekly-repeated regimen. Two randomized trials failed to show any benefit in the neoadjuvant setting with a dose-dense regimen. No evidence of a benefit was provided in metastatic breast cancer. In advanced colorectal cancer, evidence of an improvement in survival with weekly or bi-weekly 5-FU-leucovorin compared to a classic monthly schedule has recently been shown in two randomized trials, and dose-dense regimens are recognized as standard therapy in many countries. Phase II studies of dose-dense regimens have also shown high response rates and long survival in many neoplasms, including Ewing's sarcoma, gestational trophoblastic disease, ovarian carcinoma and gastric cancer. CONCLUSIONS: A considerable amount of experience has been gained with frequently-repeated regimens. A few randomized trials have demonstrated a benefit for survival on standard chemotherapy in small-cell lung cancer and advanced colorectal cancer. However, this benefit appears to be weak. The combination of dose-dense chemotherapy regimens with new anti-cancer strategies based on our insights into the mechanisms of oncogenesis is a challenge on the eve of the millennium.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Docetaxel-cisplatin combination (DC) chemotherapy in patients with anthracycline-resistant advanced breast cancer.

PURPOSE: The safety and efficacy of a docetaxel-cisplatin combination (DC) were evaluated in 41 patients pretreated for advanced breast cancer (ABC). PATIENTS AND METHODS: The first 2 patients received 85 mg/m2 docetaxel followed, 6 hours later, by 80 mg/m2 cisplatin repeated every 3 weeks; the other 39 received the same regimen, with 75 mg/m2 docetaxel. Appropriate dose reductions but no growth factor administration were planned. Treatment was continued until disease progression, excessive toxicity or patient refusal. RESULTS: A total of 223 chemotherapy courses were administered, with a median of 6 cycles per patient (range 1-8). All 41 patients were assessed for toxicity using NCI-CTC. Severe neutropenia was experienced by 38 patients (93%) (11 at grade 3, 27 at grade 4, 10 with febrile neutropenia). There was one death due to neutropenic septic shock. Grade 3 thrombocytopenia occurred in three patients (7%). Five patients (12%) had grade 2 neurosensory toxicity, two (5%) experiencing partial hearing loss. Grade 3 fluid retention occurred in three patients (7%). Of 38 anthracycline-resistant patients, 33 were evaluable for response. Two had a complete response (CR) and ten a partial response (PR), giving an objective response rate of 36%, (95% CI: 20%-55%). Stable disease (SD) was observed in 14 patients (42%), 7 (21%) had progressive disease (PD). Among the three non-resistant patients, two PRs and one SD were observed. Median duration of response was 29 weeks (range 18-70), median time to progression 21 weeks (4-70), and median overall survival 50 weeks (4-104+). CONCLUSIONS: This DC regimen is active, with an acceptable safety profile in anthracycline-resistant ABC patients. Its place as a second-line treatment alternative to docetaxel alone or to other second-line combination regimens remains to be determined.

Adult↗
PubMed1999

High-dose epirubicin and cyclophosphamide every two weeks as first-line chemotherapy for relapsing metastatic breast cancer patients.

BACKGROUND: Metastatic breast cancer remains incurable with conventional chemotherapy. For any specific chemotherapy, higher dose intensity may be achieved with either increased doses per cycle, or shortened intervals between courses, or both. We demonstrate here the feasibility and encouraging results of a high-dose combination regimen administered every two weeks. PATIENTS AND METHODS: Women with metastatic breast cancer were treated every 14 days for 6 courses with 75 mg/m2 epirubicin and 1200 mg/m2 cyclophosphamide, followed by conventionally-delivered (q 3-4 weeks) chemotherapy. The treatment was to be resumed regardless of the neutrophil count, except in instances of febrile neutropenia. Prophylactic oral antibiotherapy was given, while hematopoietic growth factors and stem cell support were not employed. RESULTS: Eighty-six patients were treated between May 1986 and June 1995. Their median age was 43 years (26-69). Grade 3-4 neutrophil toxicity was observed after 86% of the courses, resulting in febrile neutropenia in 5%-18% of the patients, and the rehospitalization of 5%-10%. The median given/planned dose intensity was 97% (79-106). The objective response rate in 84 evaluable patients was 54% (95% confidence interval (95% CI): 43-65), with a complete response rate of 11%, and a 14% rate of outright progression. Median progression-free survival was 16 months and median overall survival 32 months. Multivariate analysis retained previous adjuvant chemotherapy as a negative survival prognostic factor. CONCLUSIONS: This dose-intensive anthracycline-based regimen is feasible with manageable morbidity despite pronounced myelotoxicity, and yields encouraging survival rates.

Adult↗