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Biomedical subjects

M Spielmann

Publications and source records attributed to M Spielmann.

At least 91 records · Page 5Linked to original sources
PubMed1990

Immunohistochemical staining of bone marrow biopsies for detection of occult metastasis in breast cancer.

Immunohistochemical (IHC) techniques should allow for a greater detection of bone marrow micrometastasis in patients with breast carcinoma. We studied a series of bone marrow (BM) biopsies negative by conventional histologic techniques from 93 patients with breast carcinoma. Prior to this study, twelve BM biopsies, positive by conventional histology, were stained with a panel of monoclonal antibodies (MoAb), directed either against cytokeratin (KL1, AE1-AE3, CAM5-2) or epithelial membrane antigen (EMA, HMFG2). KL1 appeared to be the most sensitive of the markers used in the detection of metastases and is available commercially. It therefore was the only MoAb used with the series of 93 BM biopsies negative by conventional examination. Within this series, among 45 patients clinically suspected of having bone marrow metastasis but with BM biopsies negative by conventional staining, one case showing myelofibrosis stained positive with KL1 demonstrating isolated tumor cells. For the 48 patients without suspicion of bone marrow metastasis at initial diagnosis for breast carcinoma, KL1 revealed no marrow metastasis. Single bone marrow biopsy techniques whether stained by conventional or IHC methods do not appear to be useful tests to detect occult bone marrow metastasis, especially at initial diagnosis of clinically Mo breast carcinoma patients.

Antibodies, Monoclonal↗
PubMed1990

Pirarubicin in advanced breast cancer: a French cooperative phase II study.

79 patients with advanced breast cancer were given Pirarubicin 20-25 mg/m2 during 3 consecutive days every 3 or 4 weeks. 78 were evaluable for response (41 without previous chemotherapy and 37 with only one previous regimen). The overall response rate was 35% (95% CI 24-45) and the complete response rate was 8%. In previously untreated patients, the response rate reached 41.5%. The limiting toxicity was a non-cumulative granulocystopenia, sometimes severe at these high doses, with a prompt recovery. The non-haematological toxicities were mild, and included 13% with grade 3 alopecia.

Adult↗
PubMed1990

Alternating radiotherapy and chemotherapy in non-metastatic inflammatory breast cancer.

Ninety-nine patients presenting with non-metastatic inflammatory breast cancer were treated with an alternating protocol of radiotherapy and chemotherapy. The alternating schedule consisted of 8 courses of combined chemotherapy, including doxorubicin, vincristine, cyclophosphamide, methotrexate and 5-Fluorouracil, and 3 series of loco-regional radiotherapy delivering a total dose of 65 to 75 Gy to the breast tumor, 65 Gy to the axilla, and 50 Gy to the supraclavicular and internal mammary chain lymph nodes. Radiotherapy was started after the third course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy-five percent of patients were in complete remission at the end of this induction treatment. The 3-year local control was 72% and the 3-year overall survival rate was 70%. An isolated local recurrence was observed in only 4% of patients. Approximately one-half of patients developed distant metastases. These results show that alternating radiotherapy and chemotherapy schedules deserve further investigation in locally advanced breast cancer.

Adult↗
PubMed1990

A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy.

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.

Administration, Oral↗
PubMed1989

Structure and expression of c-erbB-2 and EGF receptor genes in inflammatory and non-inflammatory breast cancer: prognostic significance.

C-erbB-2 and epidermal growth factor receptor (EGFR) genes were independently shown to be associated with breast cancer progression. In this report, we have analyzed the structure and expression of these 2 genes in the same tumor specimens of a large series of breast cancers. Two clinical types of tumor were studied: inflammatory (IBC) and non-inflammatory breast cancers (NBC) obtained from 221 untreated patients at different clinical stages. Amplification and over-expression of the c-erbB-2 proto-oncogene were observed in 27% and 47% of tumors, respectively, and were strongly associated with breast cancers of the most unfavorable prognosis, namely IBC and NBC with multiple positive axillary nodes. EGFR gene was neither amplified nor rearranged. A restriction fragment length polymorphism (RFLP) for HindIII endonuclease was observed. EGFR transcripts were detected in 46% of tumors and observed more frequently in IBC than in NBC (p less than 0.02). In NBC the presence of EGFR transcripts increased linearly with lymph-node involvement and was associated with estrogen-receptor-negative tumors (p = 0.01). Analysis of both genes from the same tumor samples indicated that genes are associated with cancer aggressiveness. Furthermore, in NBC these 2 genes were independently activated, in contrast to IBC in which activated genes were negatively correlated, suggesting that c-erbB-2 and EGFR genes play different roles in NBC and IBC.

Breast Neoplasms↗
PubMed1989

Primary breast sarcoma: a review of 33 cases with immunohistochemistry and prognostic factors.

The clinical and pathological features of 33 previously untreated patients with primary breast sarcoma were retrospectively analysed to evaluate the prognostic significance of histologic variables on survival. The series comprised 17 cystosarcomas phyllodes and 16 stromal sarcomas (excluding angiosarcomas). All tumors were reviewed and classified in similar fashion to extramammary soft tissue sarcomas. In addition, immunohistochemical studies were performed on paraffin sections with a panel of several antibodies directed against cytoskeletal filaments and cellular enzymes; five cases were also examined by electron microscopy. Most tumors were malignant fibrous histiocytoma (21 cases) and fibrosarcoma (6 cases) types. Surgery was the main therapy. Metastasis-free survival rate was significantly correlated only with histological grade, consisting of tumor differentiation, tumor necrosis, and mitotic activity. Courses and survivals of the cystosarcoma and stromal groups were identical, questioning the clinical value of this pathologic distinction. All local recurrence, metastasis, or death occurred within 30 months, though follow-up was much longer. Immunohistochemistry was disappointing for identification of specific histologic sub-types.

Adult↗
PubMed1989

Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer.

A randomized trial was conducted at the Institut Gustave-Roussy (IGR) between 1972 and 1980 comparing tumorectomy and breast irradiation with modified radical mastectomy. One hundred and seventy-nine patients with an infiltrating breast carcinoma up to 20 mm in diameter at macroscopic examination were included: 88 had conservative management, and 91 a mastectomy. All patients had a low-axillary dissection with immediate histological examination. For the patients with positive axillary nodes, a complete axillary dissection was undertaken. Overall survival, distant metastasis, contralateral breast cancer and locoregional recurrence rates were not significantly different between the two treatment groups.

Adenocarcinoma↗
PubMed1989

[Treatment of inflammatory cancer of the breast. Combined chemotherapy and radiotherapy. Apropos of 270 women treated at the Institut Gustave-Roussy].

From January 1976 to January 1985, 210 patients (less than 70 years old) with unilateral inflammatory breast carcinoma M0 were treated, under protocol way, by chemotherapy, hormonotherapy and radiotherapy association. Results of these protocols are compared to those of an historical control group T (60 patients treated from 1973 to 1975 by radiotherapy alone, with castration for pre-menopausal women). From 1976 to 1980, 91 patients (group A) were treated by induction chemotherapy first with adriamycin, vincristine and methotrexate (AVM), loco-regional radiotherapy and maintenance chemotherapy with vincristine, cyclophosphamide and 5 fluorouracil (VCF). From 1980 to 1982, 79 patients (group B) were treated under a similar protocol, but the 3 first sequences were reinforced with the association of five drugs: adriamycin, vincristine, cyclophosphamide, methotrexate, 5 FU (AVCMF). From 1983 to 1985, 40 patients (group C) were treated under the same schedule AVCMF, AVM, VCF, but radiotherapy was delivered on a different schedule to shorten the intervals between the 3, 4, 5 and 6th chemotherapy sequences. All patients form the groups A, B and C had received hormonotherapy: castration for premenopausal patients or on-going menopause, or tamoxifen for post-menopausal patients. Disease-free survival rates at 30 months are respectively 19, 37, 61 and 64% for groups T, A, B and C and for groups T, A and B: 8, 22 and 40% at 5 years, and total survival rates at 5 years: 28, 40 and 55% for these groups. The benefit of chemotherapy in addition to radiotherapy is highly statistically significant. The improvement of these results seems partially linked to the increasing dosage of the induction chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Epidermoid cancer of the esophagus. Does the efficacy of chemoradiotherapy justify surgical abstention?].

Nine inoperable patients with squamous esophageal cancer were selected from 112 patients treated with combination chemo-radiotherapy. The criteria of selection were: 1) localized cancer (T1 or T2 of the TNM classification), 2) complete response after neoadjuvant chemotherapy suggesting the possibility of a good survival, 3) and 65 Gy-irradiation in the previous tumor bed. Eight of these 9 carcinomas recurred locally after a median delay of 12.6 months after the end of the treatment (extremes: 2 and 30 months). Only one patient is free of disease 24 months after the end of the treatment. These results point out that this chemo-radiotherapeutic association is disappointing in the long term in terms of loco-regional tumoral control and survival, but appeared to be good palliative treatment. This is an argument against the attitude of physicians who currently recommended a non-surgical strategy and deny the value of surgery. The carcinologic surgical excision of esophageal cancers is still the best treatment today. It must be performed whenever it is feasible, possibly associated with complementary treatments (evaluated in prospective studies).

Carcinoma, Squamous Cell↗
PubMed1989

[Epidermoid cancer of the esophagus: is the combination of chemotherapy then surgery beneficial?].

Ninety-two patients with carcinoma of the esophagus were treated with pre-operative chemotherapy (2 courses) before undergoing surgery. Chemotherapy and/or radiation were carried out after surgery depending on the tumor response to chemotherapy and extent of the tumor found at surgery. Tumor response before surgery (according to OMS criteria) was determined in 84 patients. Forty-four percent of patients showed a tumor regression of over 50%. Curative surgery was more frequently performed in patients with good tumor regression (greater than 50%) than in patients with less satisfactory tumor regression (less than 50%) (76 versus 57.5% respectively) (P = 0.08). Patients who underwent curative surgery had a lower pathologic staging when tumor regression was over 50%. However, the number of patients is too limited for any definite conclusions to be made. Survival rate at 3 years was similar in both groups of patients with curative surgery. Survival was not influenced by the extent of tumor regression before surgery. This study also suggests that the pre-operative chemotherapy did not increase the survival rate of patients who underwent curative surgery. Therefore it does not seem advisable to undertake a phase III randomized study on pre-operative chemotherapy patients.

Antineoplastic Agents↗
PubMed1988

Salvage chemotherapy in refractory germ cell tumors with etoposide (VP-16) plus ifosfamide plus high-dose cisplatin. A VIhP regimen.

Twenty-one patients with refractory germ cell tumors were treated with a chemotherapy regimen containing etoposide (VP-16) (V) 75 mg/m2/day (days 1 to 5), ifosfamide (I) 3 g/m2/day (days 1 and 2) with a 3.6 g/m2 continuous infusion of mesna (days 1 and 2), and high-dose cisplatin (hP) 40 mg/m2/day (days 1 to 5). The regimen is referred to as VIhP. Nineteen patients were evaluable for response. Five patients (26%) achieved a complete remission (CR) with chemotherapy alone, and three patients (16%) were in CR after resection of a residual nonactive tumoral mass (e.g., necrosis and/or fibrosis and/or mature teratoma). Thus, a CR rate of 42% was achieved with the entire treatment. One additional patient achieved a CR after resection of active, bulky disease. Among the responders, five patients (26%) are still alive and disease-free at 6, 7, 9, 10, and 18 months after the initiation of the chemotherapy. However, toxicity was heavy in this protocol. Severe myelosuppression was observed with 10 patients developing aplasia and six patients documented sepsis. Reversible Grade 1-2 renal toxicity occurred in 14 patients, and Grade 2-3 peripheral neurotoxicity occurred in six patients. No hemorrhagic cystitis was encountered. We conclude that a VIhP regimen seems to play an active role in refractory germ cell tumors although the presence of high-dose cisplatin in this regimen does not appear to improve the response rate compared to that of a conventional dose. Toxicity, which seems to be enhanced, is currently under detailed study. However, the contribution of VIhP as a first-line treatment in poor prognosis, advanced germ cell tumors warrants further study.

Adolescent↗
PubMed1988

Long-term effect of internal mammary chain treatment. Results of a multivariate analysis of 1195 patients with operable breast cancer and positive axillary nodes.

A multivariate analysis on 1195 patients with operable breast cancer and histologically positive axillary nodes treated by mastectomy and complete axillary dissection at the Institut Gustave-Roussy between 1958 and 1978 suggests a beneficial effect of treatment of the internal mammary chain (IMC) on the risks of death and distant metastasis for the patients with medial tumors. For these patients, surgical IMC dissection and post-operative irradiation have similar effects on both the risk of death and of distant metastasis. For the patients with lateral tumors, no beneficial effect of the treatment of the IMC on these two risks was observed. Postoperative irradiation to the IMC, axilla, chest wall and supraclavicular nodes significantly decreases the risk of locoregional recurrences independent of the tumor site and surgical management of the lymph nodes.

Adult↗
PubMed1988

c-Ha-ras-1 polymorphism in human breast carcinomas: evidence for a normal distribution of alleles.

Analysis of the c-Ha-ras-1 locus for restriction fragment length polymorphism was determined by Southern blot hybridization in 112 specimens of primary breast carcinoma. Normal cell samples were lymphocytes obtained from 61 of these breast cancer patients and from 62 healthy donors. Our data indicate that the distribution of c-Ha-ras-1 alleles in breast carcinoma patients did not significantly differ from that found in normal individuals. In addition the loss of one allele detected in 5 tumor samples was not correlated to the aggressiveness of breast cancer. Consequently our data imply that hereditary predisposition to breast cancer is not associated with the c-Ha-ras-1 polymorphism as previously reported.

Alleles↗
PubMed1988

Overexpression of either c-myc or c-erbB-2/neu proto-oncogenes in human breast carcinomas: correlation with poor prognosis.

Tumor specimens from 116 untreated patients with primary breast carcinoma at different clinical stages were analyzed for the structure and/or the expression of c-myc and c-erbB-2/neu proto-oncogenes. An amplification of the c-myc proto-oncogene (3 to greater than 50 fold) was detected only in 6% of carcinomas, with no evidence of locus rearrangement. High c-myc RNA levels detected in 45% of tumors were found significantly (p less than 0.01) correlated with lymph node involvement. Amplification (3 to greater than 30 fold) of the c-erbB-2/neu gene was observed in 20% of cancers. A 5 kb c-erbB-2/neu gene transcript was detected in the 103 cancer specimens analyzed. High levels of transcripts were observed in 36% of tumors. Overexpression did not depend only on amplification since found in 14 tumor samples with a single gene copy. The gene amplification and overexpression were found significantly associated with cancers of poor prognosis. Moreover our data show that both proto-oncogenes are overexpressed only in 12.5% of tumor samples and suggest that each gene might play a different role in tumor progression.

Blotting, Northern↗