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J M Extra

Publications and source records attributed to J M Extra.

At least 19 recordsLinked to original sources
PubMed2001

High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study.

The aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g x m(-2) and epirubicin 100 mg x m(-2) every 14 days. G-CSF 5 microg x kg(-1) x day(-1) was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with > or = 2 x 10(6) CD34+ PBSC x kg(-1) required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n = 4), severe asthenia (n = 3), haemorrhagic cystitis (n = 1). A median number of 10.8 x 10(6) CD34+ PBSC x kg(-1) (range, 3-80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72-102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit.

Adult↗
PubMed2001

Primary chemotherapy for operable breast cancer: incidence and prognostic significance of ipsilateral breast tumor recurrence after breast-conserving surgery.

PURPOSE: To determine the incidence and the prognostic value of ipsilateral breast tumor recurrence (IBTR) in patients treated with primary chemotherapy and breast-conserving surgery. PATIENTS AND METHODS: Between January 1985 and December 1994, 257 patients with invasive T1 to T3 breast carcinoma were treated with primary chemotherapy, lumpectomy, and radiation therapy. The median follow-up time was 93 months. To evaluate the role of IBTR in metastase-free survival, a Cox regression multivariate analysis was performed using IBTR as a time-dependent covariate. RESULTS: The IBTR rates were 16% (+/- 2.4%) at 5 years and 21.5% (+/- 3.2%) at 10 years. Multivariate analysis showed that the probability of local control was decreased by the following independent factors: age < or = 40 years, excision margin < or = 2 mm, S-phase fraction more than 4%, and clinical tumor size more than 2 cm at the time of surgery. In patients with excision margins of more than 2 mm, the IBTR rates were 12.7% at 5 years and 17% at 10 years. Nodal status, age < or = 40 years, and negative estrogen receptor status were predictors of distant disease in the Cox multivariate model with fixed covariates. The contribution of IBTR was highly significant (relative risk = 5.34) when added to the model, whereas age < or = 40 years was no longer significant. After IBTR, 31.4% (+/- 7.0%) of patients developed metastases at 2 years and 59.7% (+/- 8.1%) at 5 years. Skin involvement, size at initial surgery, and estrogen receptor status were predictors of metastases after IBTR. CONCLUSION: IBTR is a strong predictor for distant metastases. There are implications for conservative surgery after downstaging of the tumor and therapy at the time of IBTR.

Adult↗
PubMed2001

Response to chemotherapy is a major parameter-influencing long-term survival of metastatic breast cancer patients.

BACKGROUND: In cancer patients, correlation between response to chemotherapy and gain in survival remains debated. We addressed this question in a multivariate analysis evaluating response to chemotherapy as a factor influencing survival of patients with metastatic breast cancer. PATIENTS AND METHODS: From 1977 to 1992, 1430 patients included in eight consecutive prospective trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, were available for assessment. Median follow-up was 155 months. RESULTS: Median survival from the date of randomisation was 24 months. Objective response rate was 63.6%. A complete response (CR) was achieved in 17% (249 patients). In a stepwise forward progression analysis objective response was the first independent prognostic factor for survival. Median survival time was 43 months for complete responders (CR), 29 months for partial responders (PR), 18 months for stable disease (SD), 5 months for progressive disease (PD). The probability of survival at 5 and 10 years was 35% and 15% for CR's and decreased to 18% and 6% for PR's. The timing of best response (at 4 or 8 months) was not related to outcome. CONCLUSIONS: Response to an anthracycline-based chemotherapy is a major independent prognostic factor in metastatic breast cancer. The use of this factor to investigate new drugs seems to be pertinent. The good prognosis of complete responders justifies further evaluation of new treatment strategies for this patient population.

Adult↗
PubMed2001

Residual tumor cell contamination in peripheral blood stem cells collections of 117 breast cancer patients evaluated by immunocytochemical technique.

During the last years, high-dose chemotherapy and hematopoietic stem cell support have been thought to improve the treatment of poor-prognosis breast cancer. Nevertheless, the question remained as to whether the reinfusion of contaminating residual malignant cells could contribute to relapse. By using an immunocytochemical method, we have analyzed the tumor cell contamination of peripheral blood stem cells (PBSC) collected from advanced breast cancer patients. We studied 153 PBSC samples from 117 stage III and IV breast cancer patients and compared two screening methods-the usual microscopic observation and the automated cellular image analysis system (ACIS-assisted) screening. With manual observation, we found that 7 of 117 patients (5.9%) presented circulating epithelial tumor cells in 9 of 153 (5.8%) PBSC analyzed, whereas automated screening allowed positive detection in 15 of the same 117 patients (12.8%) and in 18 of the 153 PBSC (11.7%). No difference was found between presence or absence of circulating tumor cells and previous chemotherapy treatment (p = 0.5) or stage TNM (p = 0.13) in this group of poor-prognosis breast cancer. We did not find incidence of infusion of contaminated PBSC on overall survival or time to progression.

Adult↗
PubMed2000

[Retrospective multivariate analysis of radio-pathological correlations of nonpalpable breast lesions. Experience of the Hospital Saint-Louis].

PURPOSE: Several studies have demonstrated that systematic breast cancer screening increases overall survival. We report our experience regarding diagnosis of breast lesions detected using mammography. METHODS: Case reports of patients operated on in either 1992 or 1993 were retrospectively reviewed. A multivariate analysis of the clinico-pathological correlation was performed. RESULTS: Four hundred fifty seven patients representing on total 544 procedures, were included in the study. Mean age was 50.5 years (range 19-80 years). Most of the patients had no previous history of mammary lesion. Mammography was performed with prophylactic intent in more than 60% of the cases. Four hundred twelve (75.7%) benign lesions were diagnosed. Main lesions were: adenofibroma (15.7%), fibrocystic mastopathy (66.3%), adenosis (26.2%), ductal hyperplasia (23.9%), lobular hyperplasia (10.7%), and combined ductal and lobular hyperplasia (8.5%). Hyperplasia accompanied by cytonuclear atypia was observed in 49 (11%) cases. One hundred thirty two (24.3%) malignant lesions were reported, including 69 (52.3%) invasive carcinomas and 63 (47.7%) in situ carcinomas. Only nine axillary lymph node dissections were positive and 75 minimal breast cancers were diagnosed. The multivariate analysis showed that only radiological signs are a risk factor for cancer. The relative risk for cancer when focus of irregular and vermicular microcalcifications are diagnosed is 4.2 (2.0-8.5). It is 5.6 (2.5-12.5) in case of spiculated opacity. CONCLUSION: Exeresis following radiological prophylactic screening allows diagnosis of high-risk benign lesions and low-stage breast cancer. Radiological parameters are the most powerful predictive factors for malignancy.

Adult↗
PubMed2000

Predictive factors of response to first-line chemotherapy in 1426 women with metastatic breast cancer.

Since response to chemotherapy is a major determinant of survival in metastatic breast cancer, the purpose of our study was to analyse the predictive factors of response. 1426 patients enrolled into eight consecutive randomised trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, between 1977 and 1992, were analysed. A forward stepwise logistic regression analysis was used. The objective response rate (ORR) to chemotherapy in the total population was 63.6% (95% confidence interval (CI): 61.5-67.7). The complete response rate was 17.5%. Multivariate analysis defined adjuvant chemotherapy, lactate dehydrogenase (LDH), Karnofsky index (KI), and pleural and lung metastases to be the five main variables correlated with ORR. A predictive score was calculated using the coefficient of these five variables, The score was established as follows: -1.32+0.54 (if prior adjuvant chemotherapy) +0.80 (low KI) +0.75 (raised LDH) +0.49 (lung metastases) +0.51 (pleural metastases). A low score (less than -0.78) was associated with an ORR greater than 70.0%, representing 41.2% of our population. An intermediate score (between -0.78 and 0) was associated with an ORR of 50 to 70%, representing 37.5% of our population and a positive score was associated with an ORR of less than 50%, representing 21.3% of our population. This score can be used to predict objective response rates to first-line anthracycline-based chemotherapy. This method now needs to be evaluated prospectively in phase II trials. Identification of various risk groups may also be useful for interpretation and design of clinical trials.

Adult↗
PubMed2000

Prognostic value of persistent node involvement after neoadjuvant chemotherapy in patients with operable breast cancer.

Neoadjuvant chemotherapy is able to reduce the size of the majority of breast tumours and down-stage axillary-node status. The aim of this study was to assess the prognostic value of persistent node involvement after neoadjuvant chemotherapy. A total of 488 patients with T2-T3, N0-N1 breast cancer treated by neoadjuvant chemotherapy followed by tumour excision and axillary lymph-node dissection between 1981 and 1992 were selected from the Institut Curie database. Median follow-up was 7 years. Overall objective response rate before local treatment was 52% and breast tumour size was reduced in 83% of patients. No pathologic nodal involvement was observed in 46. 5% of patients. Patients with > or = eight positive nodes had a very poor median disease-free survival of only 20 months. Their 10-year disease-free survival rate was 7%, while the 10-year disease-free survival rate for patients with no node involvement was 64%. Median survival for patients with > or = eight nodes positive was 48 months and the 10-year survival rate was 26% (P < 0.0001). On multivariate analysis, outcome was strongly correlated with pathological nodal status, tumour grade, hormonal receptor status and clinical response of the tumour. In conclusion, patients with extensive nodal involvement after neoadjuvant chemotherapy have a very poor outcome. Second-line treatment should be considered in this population.

Adult↗
PubMed2000

Detection of MUC1-expressing mammary carcinoma cells in the peripheral blood of breast cancer patients by real-time polymerase chain reaction.

We have prospectively analyzed blood samples of 122 patients with breast disease for the presence of circulating expressing MUC1 cells before and after treatment. Among them, 28 patients had histologically confirmed benign breast disease (group 1), 34 patients had operable breast cancer (group 2), and 60 patients had advanced breast cancer (group 3). Circulating epithelial cells were isolated with BerEP4-coated immunomagnetic beads. Total RNA was extracted and reverse transcribed before analysis by real-time PCR of a MUC1-specific cDNA sequence. The sensitivity of the reverse transcription-PCR tested with blood spiked with MCF7 cells was one cell in 5 ml of blood. The immunomagnetic separation step was mandatory to obtain the maximum specificity. Control samples from healthy donors never displayed cycle threshold (Ct) values for MUC1 lower than 38. Circulating cells (Ct, <38) were detected in 3 of 28 (11%) cases in group 1, in 8 of 34 (24%) cases in group 2, and in 27 of 60 cases (45%) in group 3. A semiquantitative estimate of blood-borne cells could be derived from the Ct value when below 32 (the lowest was 28) or by the number of positive aliquots of the same blood sample. Thus, immunomagnetic separation, followed by MUC1-specific RT-PCR, allows the semiquantitative detection of circulating mammary cells. A significant correlation between the presence of MUC1-positive cells and the group of breast tumors was observed. The clinical significance of blood-borne cells in breast cancer, especially at the operable stage, may be investigated by following these patients.

Adult↗
PubMed2000

[How to finance chemotherapy with new cancer drugs?

Recently developed drugs are ten to one hundred fold more costly than the chemotherapies of the past while the number of eligible patients and the average duration of treatments are ever increasing. The combined effect of these trends makes budgeting a daunting task, in particular for hospitals with budgetary allocation. Balancing budgets became difficult with the arrival of taxanes, but innovative therapies based on biotechnological advances will further increase the financial slide. Hospital running costs can not be infinitely reduced. Therefore, new rules that govern the financing of innovative therapies become mandatory and budgetary allocations based on DRG evaluations will no longer be feasible.

Antineoplastic Agents↗
PubMed1999

Urinary carboxyterminal telopeptide of collagen I as a potential marker of bone metastases chemotherapy monitoring in breast cancer.

Breast cancers frequently have osteoclastic bone metastases that are difficult to monitor and treat. Bone scintigraphy with 99mTc-labeled biphosphonates is still the reference method for detecting and localizing bone involvement. Classical biochemical markers such as urinary calcium have poor sensitivity for detecting and monitoring metastases of breast cancers. New biochemical markers for the study of bone remodeling have recently been developed, including a degradation product of the C-terminal end of the telopeptide of type I collagen (CTX). We used an immunoenzymatic assay technique for urinary CTX in 84 pre- and post-menopausal women and demonstrated a correlation between scintigraphic scores and urinary CTX concentrations. CTX values are significantly different between the control group and patients with bone metastasis, except those with score 0. There is a regular increase in urinary CTX concentration from score 0 (no abnormal uptake) to score 4 (diffuse carcinomatosis). There is no significant variation between control population and score 0 to 3 for urinary calcium. Only women with scintigraphic score 4 have significantly increased urinary calcium concentrations. Measuring CTX in pre- and post-menopausal patients during breast cancer chemotherapy might be of great interest for monitoring the development of metastases and the therapeutic efficacy of chemotherapy.

Adult↗
PubMed1999

Oxaliplatin and paclitaxel combination in patients with platinum-pretreated ovarian carcinoma: an investigator-originated compassionate-use experience.

PURPOSE: Compassionate-use oxaliplatin paclitaxel was assessed for toxicity and efficacy according to clinical platinum resistance status in cisplatin-carboplatin-pretreated advanced ovarian cancer patients. PATIENTS AND METHODS: Thirty-seven patients, retrospectively grouped into four oxaliplatin-paclitaxel dose levels (mg/m2): (DL1: 100/135; DL2: 130-135/135; DL3: 100/160-175; DL4: 130-135/160-175), received oxaliplatin and paclitaxel every three to four weeks. RESULTS: Thirty-one of thirty-seven treated patients were evaluable for activity, with 1 complete and 14 partial responses, (objective response rate: 48%, 95% CI: 31-66). Of 18 platinum-resistant patients 6 responded, and of 13 platinum-sensitive patients, 9 responded. One patient (3%) had two febrile neutropenia episodes, and eight (22%) and eleven patients (30%) had grades 3 and 4 neutropenia, respectively. Six patients (16%) experienced grade 3 peripheral neuropathy. The median response duration was 10.8 months, with a 23-month (range 8-54) median follow-up. Median progression-free and overall survivals were 9 months (95% CI: 7-12), and 25.2 months (95% CI: 12-39), respectively. CONCLUSIONS: The antitumour activity of oxaliplatin-paclitaxel in platinum-resistant ovarian cancer patients accords with experimental data on the agents' lack of cross-resistance. Time-related progression parameters confirm it as a promising salvage treatment option.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed1998

Is p53 a protein that predicts the response to chemotherapy in node negative breast cancer?

The role of p53 in modulating apoptosis has suggested that it may affect efficacy of anti cancer agents. For this reason, we have evaluated p53 alterations in 282 consecutive patients with infiltrating node-negative breast cancer who underwent primary surgery and were randomized either to CMF (Cyclophosphamide 400 mg/m2, Fluorouracil 400 mg/m2, and Methotrexate 40 mg/m2) or control arm (no adjuvant therapy) from 1980 to 1989. p53 alterations were analyzed by immunohistochemistry using DO7 MoAb, revealed by immunoperoxidase technique, and quantitated in term of percentage of positive cells. We observed a positive staining in 24% of the tumors. Among them, 10% had a positive staining in more than 75% of the cells. There was a highly significant association between the proportion of positive cells and histologic grade of the infiltrating ductal carcinomas (p<0.004). However, there was no association with age, tumor size, hormone receptor content, or vascular embolism. There was a trend but no significant relationship between positive staining and overall survival either in each arm of the trial or in the overall population. Interestingly, we observed a higher relative risk of local relapse after conservative therapy in the boosted area in the group of mutated p53 (RR=4.41; p<0.0005). We conclude that, in this node-negative breast tumor population, alteration of p53 cannot predict the response to the chemotherapy. However, it may represent a useful marker of risk of local relapse and of radio resistance.

Adult↗
PubMed1998

Pharmacokinetics and safety profile of oxaliplatin.

In early clinical trials, oxaliplatin has demonstrated significant activity against colorectal cancer, both as a single agent and in combination with 5-fluorouracil (5-FU) and folinic acid (FA). Oxaliplatin differs from cisplatin in its lack of nephrotoxicity and from carboplatin in its hematologic toxicity being mild. The most constant acute side effect of oxaliplatin observed in clinical trials was a transient peripheral neuropathy manifesting as paresthesia and dysesthesia in the extremities, triggered or enhanced by exposure to cold. The neurosensory phenomena, dependent on the cumulative dose of oxaliplatin, affect all patients who receive doses > or = 540 mg/m2 over four cycles or more of therapy. This neurologic toxicity is also highly reversible, with 82% of patients having their neuropathy regress within 4 to 6 months and 41% experiencing complete recovery within 6 to 8 months. With these considerations in mind, the currently recommended dosing schedules for oxaliplatin are 130 mg/m2/d as a 2- to 6-hour infusion or 175 mg/m2/d as a chronomodulated infusion over 5 days, both of which are administered every 3 weeks. Oxaliplatin rapidly disappears from the plasma and is rapidly transformed into putative active species. 5-Fluorouracil and folinic acid, often used in combination with oxaliplatin, do not affect its pharmacokinetics. The favorable pharmacokinetics and safety profile of oxaliplatin contribute to its tolerability, particularly in pretreated cancer patients with reduced renal function. The reversible nature of its dose-limiting neurotoxicity and its synergistic action with 5-FU/FA make oxaliplatin an interesting agent for the treatment of colorectal cancer and for other potential indications.

Antineoplastic Agents↗
PubMed1998

[Clinical activity spectrum of irinotecan].

Irinotecan (CPT11), a topoisomerase I inhibitor, is a new cytotoxic agent with a broad spectrum of clinical activity. Two main schedules have been studied and produce similar activity and side-effects: the "european" one--350 mg/m2 every 21 days-, and the "japanese-north american" one where CPT11 is given at a weekly dose of 100-120 mg/m2 for 4 consecutive weeks followed by a 2 week rest period. Activity was initially characterized in advanced colorectal cancers; response rates, disease free-survival and overall survival were 11%, 7-10 months and 8-11 months in patients failing fluoropyrimidine based chemotherapy--statistically improved as compared to best supportive care and infusional fluorouracil-, and 20-30% in patients not previously treated. An interesting activity with response rates of 20-22% (increased to 65% in combination with CDDP) has been shown in relapsed cervix carcinomas; in gastric carcinomas response rates of 20% have been shown, reaching 48% in combination with CDDP. Response rates of 20-22%, increased to 40-60% when irinotecan was associated to CDDP have been reported in non small cell lung cancer and esophagal carcinomas. Further studies are needed for other GI tract cancers, ovarian and head and neck carcinomas while minimal or no clinically meaningful activity has been reported in advanced breast cancer, and haematological malignancies. Irinotecan can be combined to fluoropyrimidines, raltitrexed, cisplatin, carboplatin and oxaliplatin, to gemcitabine, etoposide, vinorelbine and taxanes with flexible schedules (weekly, every 2 weeks, every 21 days. Most of these combinations have an additive or supra additive activity. Its mechanism of action, the spectrum of activity and the acceptable risk-benefit ratio point to irinorecan as a major advance in the field of cytotoxic anticancer therapy.

Adenocarcinoma↗
PubMed1997

[Second line treatments of cancers of the ovary].

Ovarian adenocarcinomas are among the most chemosensitive tumors. Platinum derivatives are the most efficient agents. The role of the second-line therapy is either to treat the relapse (salvage therapy), or to prevent it (consolidation therapy). The most active agents in the salvage setting are new molecules: taxoids, vinorelbin, topotecan. Classical agents such as hexamethylmelamine or epirubicin are still worth of use. Reintroduction of platinum derivatives (oxaliplatin) and associations combining new and classical cytostatic agents are still on study. Consolidation treatment may use platinum-based intraperitoneal chemotherapy, and most promising results have been achieved with high-dose alkylating chemotherapy followed by haematopoietic stem-cell reinjection.

Adenocarcinoma↗