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Biomedical subjects

J Rouesse

Publications and source records attributed to J Rouesse.

At least 19 recordsLinked to original sources

[Treatment of breast cancer after 70 years of age. Report of 1143 cases].

STUDY AIM: Breast cancer is the most frequent type of cancer in women, increasing in frequency with the elderly. In Europe, a third of new breast cancers occur in women over 70 years of age. The aim of this retrospective study was to analyse the tumoural lesions and therapeutic results in a female population over 70, treated in the same medical centre over a 15-year period. PATIENTS AND METHODS: From 1978 to 1992, 1,143 female patients aged 70 or over were treated for a unilateral breast cancer without metastases and followed-up during a mean 6-year period. The initial treatment was surgical in 1,012 patients: radical mastectomy in 95% of the cases with axillary node dissection in 97.6%. Adjuvant radiotherapy was performed in 289 patients and adjuvant treatment with Tamoxifen in 411 patients. The results were compared with those obtained in 2,947 patients aged 50 to 69, treated during the same period in the same medical centre. RESULTS: The 5-year survival rate in women 70 and over was 80% vs 85.5% in women aged 50 to 69 (P < 0.000001). The same rate of loco-regional recurrences and metastases occurred in both populations. In the patients who initially underwent surgery, after multivariate analysis according to the Cox model, the prognosis factors (similar to those observed in the group of younger women) were: the number of involved nodes (P = 0.000001), the clinical size of the tumour (P = 0.00001), the histological grade (P = 0.01), and the estrogen receptors (P = 0.02). CONCLUSIONS: In this series, the treatment was focused on surgery complemented with adjuvant radiotherapy according to node invasion and adjuvant hormonotherapy according mostly to hormonal receptors. However, the complete treatment could not be applied to all cases: only 50% of patients with node involvement were irradiated. The 5-year survival rate lower than that of younger patients may be attributed to incomplete adjuvant treatment. Specific controlled trials taking into account quality of life had to be undertaken in elderly patients in order to adjust the treatment in relation with the patients' age and physiological condition.

Age Factors↗

Mitomycin-vinorelbine as second line chemotherapy in metastatic breast cancer

Fourty-six patients (41 evaluable) were treated in second line chemotherapy of metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors were estrogen receptors positive and 17% progesterone receptors positive.eventeen patients received an adjuvant chemotherapy and 39 a first line chemotherapy with anthracyclin (A). The median number of metastatic sites was 2 (1-4) and 27 patients (67%) had visceral metastases. Twelve patients were refractory to anthracyclins and 5 resistant. No toxic death nor hemolytic uremic syndrom were observed.even (3,7%) febrile neutropenias happened responsible for 4 hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective response (OR) was 37,5% with 2 complete responses (CR) and 13 partial responses (PR).even patients had stable disease and 18 progressed. The rate of hepatic OR was 31%. Five (40%) A-refractory patients responded but no resistant patient. Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6). Median survival was 11,5 months. MV association is well tolerated and effective in second line chemotherapy for MBC even with hepatic metastasis and in patients refractory to anthracyclins.

Journal Article↗

Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

PURPOSE: To evaluate the benefit of adjuvant chemotherapy in adult patients with soft tissue sarcomas. The principal end points were freedom from local recurrence and/or metastases and overall survival. PATIENTS AND METHODS: Between January 1977 and June 1988, 468 patients entered this randomized study and 317 were considered eligible. Following complete surgical resection with or without radiotherapy, outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses was compared with that in 172 control patients. RESULTS: With a median follow-up duration of 80 months (range, 39 to 165), actuarial percentage survival figures at 7 years were compared. Relapse-free survival rates were higher for CYVADIC, 56% versus 43% (P = .007), and local recurrence was significantly reduced in the CYVADIC arm at 17% versus 31% (P = .004). In contrast, distant metastases occurred with similar frequency in both arms, 32% for CYVADIC versus 36% for control patients (P = .42), and overall survival rates were not significantly different at 63% versus 56% (P = .64). A reduction in local recurrence was only apparent in the group of head, neck, and trunk sarcomas (P = .002), but not in limb tumors (P = .31). CONCLUSION: Adjuvant chemotherapy with CYVADIC cannot be recommended outside the context of a clinical trial. Experience from this study has been used to plan a trial of neoadjuvant chemotherapy with doxorubicin/ifosfamide, which is currently in progress.

Adolescent↗

Phase II trial of vinorelbine/doxorubicin as first-line therapy of advanced breast cancer.

PURPOSE: The study investigated the therapeutic effects of a combination of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Médicament, Boulogne, France) and doxorubicin in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Ninety-seven patients with progressive and assessable advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered onto the study. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients were excluded because they did not meet entry criteria or because of protocol violations. Navelbine was administered at 25 mg/m2 by 30-minute intravenous (IV) infusion on days 1 and 8, and doxorubicin at 50 mg/m2 by slow IV infusion on day 1, with each course repeated at 3-week intervals. Patients were treated for a maximum of 11 cycles or until progression or major toxicity. RESULTS: Objective responses were observed in 66 of 89 assessable patients (74%; 95% confidence interval, 63% to 85%). There were nineteen (21%) complete responses (CRs) and 47 (53%) partial responses (PRs). In addition, 20 patients (22.5%) had stable disease and three (3.5%) progressed while on treatment. Responses were observed at all sites of metastatic disease. Forty-one of 58 patients with visceral disease responded (71%) and 25 of 31 with soft tissue and bone disease experienced an objective response (81%). The median duration of response was 12 months (range, 2.4 to 40.5), and the median overall survival was 27.5 months (range, 4 to 46). Neutropenia was dose-limiting, with 36 patients (41%) experiencing grade 3 or 4 toxicity. Of 727 cycles administered, there were 20 admissions (3%) for treatment of febrile neutropenia, involving 14 of 89 patients (16%). Treatment-related cardiotoxicity at grade 2 to 4 was experienced by 10% of patients and necessitated the interruption of treatment in 1.5% of cycles. Other side effects were uncommon or manageable by conventional means. CONCLUSION: The encouraging response rates and duration achieved with this combination of Navelbine/doxorubicin under the conditions of this study deserve further randomized comparative trials with standard regimens.

Adenocarcinoma↗

Granulocyte-macrophage colony-stimulating factor allows safe escalation of dose-intensity of chemotherapy in metastatic adult soft tissue sarcomas: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

PURPOSE: This study was designed to test the feasibility of administering doxorubicin at an optimal dose-intensity (> 70 mg/m2 per 21 days) in combination with ifosfamide under recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) cover in patients with metastatic soft tissue sarcomas. PATIENTS AND METHODS: One hundred four eligible patients (of 111 entered) in 16 centers received doxorubicin 75 mg/m2 plus ifosfamide 5 g/m2 every 3 weeks for up to seven cycles. rhGM-CSF (250 micrograms/m2) was administered once or twice daily by subcutaneous injections for up to 14 days between cycles of chemotherapy. RESULTS: Full protocol dose-intensity of chemotherapy was administered to the majority of patients with only 15 of 293 cycles being complicated by febrile episodes that required hospitalization. There were two treatment-related deaths: one from septicemia and one from cardiac failure. The main toxicities attributed to rhGM-CSF were pruritus and rash. A 45% response rate (10% complete remission [CR]) was seen, with a median response duration of 9 months and median survival of 15 months. CONCLUSION: This high-dose regimen of chemotherapy was feasible under rhGM-CSF cover and produced a higher response rate and median survival than previously seen by the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue Sarcoma Group. A randomized phase III study is now underway comparing this regimen with conventional-dose doxorubicin/ifosfamide to test the dose-response relationship.

Adult↗

The use of recombinant human granulocyte-macrophage colony-stimulating factor with combination chemotherapy in the treatment of advanced adult soft-tissue sarcomas: early results from the EORTC Soft-Tissue and Bone Sarcoma Group.

We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial.

Adult↗

A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup.

PURPOSE: A randomized pilot study was undertaken to assess the acute and chronic toxicities of two short intensive chemotherapy regimens, and to evaluate the feasibility of conservative surgery in this setting. Additional aims were to determine the clinical and radiologic response and the degree of histologic necrosis after chemotherapy. With extension of the study, eventual accrual was sufficient to compare disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: Between July 1983 and December 1986, the European Osteosarcoma Intergroup (EOI) entered 198 eligible patients with classic high-grade extremity osteosarcoma onto a randomized trial that compared doxorubicin (DOX) 25 mg/m2/d times three, intravenous (IV) bolus plus cisplatin (CDDP) 100 mg/m2, 24 hour infusion, every 3 weeks times six; the same combination was preceded 10 days earlier by high-dose methotrexate (HDMTX) 8 g/m2, 6-hour infusion, every 4.5 weeks times four. In the majority of patients (179), chemotherapy was commenced after biopsy; definitive surgery was scheduled at 9 weeks in both groups. RESULTS: Toxicities for both regimens did not differ substantially from those that occurred in other trials of adjuvant chemotherapy in osteosarcoma. Local recurrence (9%) and surgical complications (18%) after conservative surgery were acceptable. With a median follow-up of 53 months, DFS at 5 years is superior (P = .02) for DOX/CDDP, 57% versus 41%, although OS, 64% versus 50%, is not different significantly (P = .10). In a subset of 66 patients for whom pathologic data on the resected specimen were available, DFS (P = .003) and OS (P = .008) were better for those who demonstrated > or = 90% necrosis. CONCLUSION: A brief intensive chemotherapy regimen of DOX/CDDP has produced excellent long-term results, which are similar to those that have been achieved in cooperative group studies of longer, more complex multiagent chemotherapy, and provide the basis for a direct comparison in the next EOI study.

Adolescent↗

[Metastases from cancers of unknown primary site. Data from 302 autopsies].

The autopsies of 302 patients who had metastases from cancers of unknown primary site were studied. In two-thirds of the cases the metastases were located in the lymph nodes, the lungs and the bones. The primary tumour was found in 82 patients when still alive (27 percent) and in 173 patients (57 percent) at autopsy. It could not be identified in 16 percent of the cases. The primary tumours most often discovered were in the pancreas (26.5 percent), the lungs (17.2 percent), the kidneys (4.6 percent) and the colorectal bowel (3.6 percent). On the whole, the paraclinical examinations performed for diagnostic purposes had been disappointing. The survival rate was the same whether or not the primary tumour had been identified. The number of inaugural metastases seems to be a major prognostic factor. These highly progressive tumours must represent a very distinct clinical and biological neoplastic entity. A simple approach and a unicist practical management are suggested.

Adolescent↗

[Cancer of the ovary after cancer of the breast. 45 cases].

Forty-five patients who had primary cancer of the breast had a laparotomy when a second cancer appeared in the ovaries. There were no other peritoneal metastases to suggest that it was disseminated breast cancer. Twenty-eight had primary ovarian cancer and 17 metastases from breast cancer. The study comparing the two groups shows that: there are few clinical or paraclinical features that make it possible to arrive at a differential diagnosis; ovarian metastases occurring in patients who have primary breast cancer carry a more serious prognosis; if the cancer is a primary ovarian cancer (and not a secondary) the chances of survival are less poor; in primary ovarian cancer the results justify our attitude for carrying out surgery; screening systematically for ovarian involvement by using CA 125 or by routine ultrasound does not seem to us to be effective.

Adult↗

Predicting distant metastases in operable breast cancer patients.

Risk factors for distant metastases following mastectomy and axillary node dissection for breast cancer were analyzed in a review of 1022 women. From diagnosis until the end of the adjuvant treatment, six stages were identified that corresponded well to patient data acquisition. At each stage, a prognosis study based on the Cox model was carried out using all acquired information from the first stage. The results demonstrated that tumor size, nuclear pleomorphism, mitotic index, and nodal status at the top of axilla were stable independent risk factors in predicting metastasis-free survival (MFS). These analyses also revealed those factors that were significantly related to MFS at one or several stages and losing their significance at a subsequent stage. This was the case with clinical node status, age, and vascular tumor emboli. Other factors such as estrogen, progesterone, histologic grade, and clinical stage were never identified as independent factors at any stage. The four major stable risk factors were used to define a stratification of reference. The results demonstrated that the mere knowledge of clinical information such as tumor size, clinical node status, and age would enable 51% of the patients to be universally well classified according to that stratification. Knowledge of additional factors, such as nuclear pleomorphism and mitotic index, would bring the rate up to 61%, and then to 64% if supplementary information such as vascular tumor emboli were acquired. These percentages did not appear high enough to claim that the physician may make a reliable prognosis of operable breast cancer patients before acquiring information from the axillary node dissection. However, it was proven that there exist some subsets of patients with stable prognosis, i.e., subsets of patients who will belong permanently to the same risk group through the stages.

Adult↗

Survival effect of systemic therapy on patients developing metastatic breast carcinoma.

A multivariate analysis was performed to assess the effect of post-relapse systemic therapy on a series of patients with metastatic breast cancer who at initial presentation had no detectable metastases (Mo), were less than or equal to 70 years of age, presented with unilateral localized disease and no other associated malignancy, and were treated between 1965 and 1984 with successive protocols for primary disease and subsequently developed distant metastasis. All 760 patients analyzed relapsed with at least one metastasis, and were studied retrospectively with no selection criteria according to any specific protocol. All had recorded clinical data on menopause, stage, clinical tumor aggressiveness (PEV), initial chemo or hormonal therapy, and time to relapse, and had ongoing follow up at our Center, with salvage chemotherapy and/or hormonal therapy having been given to some but not all patients. A brief metastasis-free survival (p less than 0.000001), and factors associated with electing pre-relapse chemotherapy (p less than 0.000001) were associated with shortened post-relapse survival, while post-relapse therapy (chemo p less than 0.0001, and hormonal p less than 0.00001, replacing chemotherapy in the model) apparently increased post-relapse survival in the group overall. This result was similar in the inoperable patient group [with inflammatory breast carcinoma an additional risk factor (p less than 0.0005)], as well as the operable group. However, in the operable group, when the pathologic criteria of histologic grade and nodal status were introduced into the analysis, post-relapse therapy was not seen to be an important factor for survival in any subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phase II trial of methotrexate-FAM (m-FAM) in adenocarcinoma of unknown primary.

Nineteen patients with adenocarcinoma of unknown primary were treated with the m-FAM regimen, consisting of methotrexate 50 mg/m2 days 0, 28; 5-fluorouracil 600 mg/m2 days 1, 8, 29, 36; Adriamycin 30 mg/m2 days 1, 29; and mitomycin-C 10 mg/m2 day 1. All drugs were recycled every 56 days. No complete responses were seen. Seven patients (37%) achieved partial remission for a median duration of 11 months. An additional nine patients (47%) had stable disease for a median duration of 6 months. Median survival for responders was 16 months and was 10 months for those with stable disease. Toxicity was acceptable. This Phase II study attempted to evaluate the clinical impact of the pharmacological modulation of 5-fluorouracil with methotrexate, the goal being improvement of the results of FAM alone in adenocarcinoma of unknown primary. However, the addition of methotrexate, at least in the schedule employed in this study, did not appear superior to FAM.

Adenocarcinoma↗

[Response of bone metastases to medical treatment: definition of evaluation criteria and classification trials].

Bone metastases are very frequent. Some are sensitive to the action of anticancer drugs. However, there is as yet an unsolved methodological problem in the evaluation of response to these drugs. The uniquely radiological UICC criteria are quite insufficient, in as much as they appear with a long delay and sometimes give erroneous results. In this work we give a brief review of biological and clinical knowledge about bone metastases, and we attempt to give an array of the possible evaluation criteria and their respective value. We propose as a working hypothesis a classification of responses taking into account the criteria: the urinary hydroxyproline to urinary creatinine ratio, the serum dosage of bone isoenzyme of alkaline phosphatase and propeptide of type III procollagen (P III NP), and as an essential element, an analysis of all available imaging techniques. A visual study of bone scintillation scans must precede that of radiographs and, when possible, it must be associated to computerized scintillation scanning. When metastasis are located to the pelvis, the vertebral column, or the sternum, a CT scan or better, a nuclear magnetic resonance study (IRM), is indispensable in order to have a direct measure of the tumor extension to soft tissues. Furthermore, in the case of isolated metastases, one of these imaging techniques allows a diagnostic biopsy. Finally an analysis of response at the bone level will always be associated with a measure of their duration and an evaluation of metastases to other sites.

Acid Phosphatase↗

Interim report of phase II study of new nitrosourea S 10036 in disseminated malignant melanoma.

Thirty-three patients with disseminated malignant melanoma were entered in a phase II study of the new nitrosourea S 10036 using a 100-mg/m2 weekly induction schedule for 3-4 consecutive weeks. Patients who responded to this treatment were followed with a maintenance therapy every 3 weeks. Toxic effects were mainly hematological and consisted of delayed thrombocytopenia and leukopenia. Among 30 patients who could be evaluated, eight partial responses were observed (response rate, 26.67%); among seven patients with cerebral metastasis, two partial responses were observed. This multicentric study is currently being continued to confirm this interim report.

Antineoplastic Agents↗

Review of the clinical trials activity of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer.

Despite the low incidence of sarcomas, the Soft Tissue and Bone Sarcoma Group has established itself as one of the more active cooperative groups of the European Organization for Research and Treatment of Cancer. Performing over a 10 yr period three phase III protocols (total entry 750 patients), three randomized phase II studies (464 patients), a pilot combination study (185 patients), and 12 phase II studies (406 patients). The new randomized phase III protocol for advanced soft-tissue sarcoma will provide an interesting test of the validity of the current membership policy, which has not discouraged the participation of enthusiastic new members. For extremity sarcomas, improved surgical techniques have increased the number of patients retaining functional limbs but have maintained excellent rates of local control. However, systemic metastasis remains a significant problem and presents a challenge for future adjuvant studies.

Adult↗