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Biomedical subjects

J Estape

Publications and source records attributed to J Estape.

At least 19 recordsLinked to original sources
PubMed2006

Continuous versus intermittent tamoxifen versus intermittent/alternated tamoxifen and medroxyprogesterone acetate as first line endocrine treatment in advanced breast cancer: an EORTC phase III study (10863).

BACKGROUND: Continuous ligand depletion of endocrine responsive tumours may enhance resistance to therapy. Intermittent treatment with tamoxifen (T) was considered to mimic (incomplete) ligand depletion and reintroduction. Furthermore it was postulated that alternating tamoxifen with a non-cross resistant endocrine modality could (further) postpone hormone resistance. PATIENTS AND METHODS: Postmenopausal patients with advanced breast cancer who did not progress after 4 months of first line T therapy were randomised to continue T (40 mg daily) or to 2 monthly intermittent T or intermittent/alternated T and medroxyprogesterone acetate (MPA, 300 mg daily). At progression during break or during MPA, T should be reintroduced. Endpoints of the study were progression free survival (PFS), time to resistance to tamoxifen and overall survival (OS). RESULTS: Of 593 registered patients, 276 were randomised. After 8 years follow-up the median PFS for continuous T, intermittent T and intermittent/alternated T and MPA was 11.0 (8.1-15.2), 8.0 (6.2-12.4) and 10.8 (7.1-16.7) months, respectively (NS). Resistance to tamoxifen was established only in 84%, 70% and 55% of patients in the three treatment arms, respectively. The median times from randomisation to resistance to tamoxifen were 12.5 (9.1-21.1), 13.2 (8.8-19.8) and 24.0 (16.9-60.9) months, respectively (p<0.001), without translation in differences in survival times. CONCLUSION: Intermittent T or intermittent/alternated T and MPA had no impact on PFS or OS as compared with classical continuous T in patients with advanced breast cancer. Intermittent/alternated T and MPA resulted in prolonged time to resistance to T, but this might partly be due to bias by omittance of the proof of tamoxifen resistance in a high proportion of the patients in this treatment arm.

Adult↗
PubMed1998

c-erbB-2 oncoprotein, CEA, and CA 15.3 in patients with breast cancer: prognostic value.

The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 healthy subjects, 58 patients with benign breast diseases, and 413 patients with breast cancer (186 locoregional, 185 with advanced disease, and 42 with no evidence of disease). Using 15 U/ml as the cut-off, no healthy subjects or patients with benign diseases and only 2.4% of no evidence of disease patients had elevated serum levels. Abnormal c-erbB-2 levels were found in 29% (101/370) of the patients with breast carcinoma (locoregional 9%, metastases 45.4%). CEA (cut-off 5 U/ml) and CA 15.3 (cut-off 35 U/ml) sensitivity was 18% and 16% in patients with locoregional disease and 61% and 70% in those patients with advanced disease, respectively. A trend toward higher serum levels of all three tumor markers in patients with nodal involvement or greater tumor size was found, but was statistically significant only with CEA (p < 0.01). By contrast, c-erbB-2 was related to steroid receptors, in both locoregional and metastatic tumors. When the prognostic value of these markers was evaluated, patients with abnormally high presurgical CEA and c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative (p < 0.05 and p < 0.001, respectively) and node-positive patients (p < 0.556 and p < 0.001, respectively). By contrast, no relationship was found between CA 15.3 values and prognosis. Multivariate analysis showed that CEA and c-erbB-2 were also prognostic factors. The correlation between serum and tissue levels of c-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). Serum concentrations in patients with advanced disease were related to the site of recurrence, with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum levels seem to be a useful tumor marker in the prognosis of patients with breast cancer. Using all three tumor markers, sensitivity was 35% in patients with locoregional breast cancer and 88% in patients with recurrence.

Biomarkers, Tumor↗
PubMed1996

Glutathione-S-Transferase M1 and codon 72 p53 polymorphisms in a northwestern Mediterranean population and their relation to lung cancer susceptibility.

Several polymorphic genes have been reported to be possibly involved in modifying lung cancer risk in smokers. The gene GSTM1 is frequently deleted in human populations, and the null genotype has been reported to be a risk factor for developing lung carcinoma. A germline polymorphism of p53 with a single-base change at codon 72 that causes an amino acid replacement of arginine (Arg; CGC) by proline (PRO; CCC) has also been reported to be associated with cancer susceptibility in a Japanese population. Both polymorphisms were genotyped by PCR in a northwestern Mediterranean healthy population (n = 147) and in a group of lung cancer patients (n = 139). The results showed that the frequency of the GSTM1 null genotype was higher in the lung cancer patients compared to the controls [odds ratio (OR), 1.57; 95% confidence interval (CI), 0.99-2.51]. The histological subtypes most clearly modified were small cell carcinoma (OR, 1.89; CI, 0.97-3.65) and adenocarcinoma (OR, 1.93; CI, 0.90-4.14). The null GSTM1 genotype was more frequent among those cancer patients who were medium/ light smokers (< or = 50 pack-years) and in those who showed an onset of the disease at a more advanced age. The study of the p53 polymorphism in the healthy population showed allele frequencies of 0.79 (Arg) and 0.21 (Pro). The frequencies found in the lung cancer patients were statistically similar. Both polymorphisms were studied together, and the relative risk of the combination null GSTM1 and Pro/Pro or Arg/Pro genotypes was calculated taking the combination of GTSM1 + together with Arq/Arg as a baseline. The OR found (1.97; CI, 1.03-3.73) suggests that the Pro allele of the p53 germline polymorphism may slightly increase the risk fo the GSTM1 null genotype among smokers.

Adenocarcinoma↗
PubMed1994

Lung cancer and cigarette smoking in women: a case-control study in Barcelona (Spain).

A case-control study on lung cancer and the habit of cigarette smoking was carried out in Barcelona (Spain). Cases were 103 women newly diagnosed with primary lung cancer in 10 hospitals from the study area. Histologic confirmation was given in 101 cases, of which 53 were adenocarcinoma, 19 squamous-cell carcinoma, 9 small-cell carcinoma and 20 other types. Two controls per case were selected, matched by age, residence and hospital. Compared with the never-smokers, the odds ratios (OR), with corresponding 95% confidence intervals (CI), were 1.61 (0.4 to 6.9) for ex-smokers and 3.61 (1.6 to 8.3) for current smokers. The risk of lung cancer showed a good dose-response relationship with duration of the habit, average number of cigarettes smoked daily and cumulative cigarette consumption. The risk of lung cancer increased by 62% for each 10 pack-years. Depth of inhalation also showed a remarkable effect, independently of the intensity of the habit. Although mortality and incidence rates of lung cancer among women in Spain are lower than in other developed countries, the risk of lung cancer is that which would be expected according to the pattern of the smoking habit in Spanish women.

Adult↗
PubMed1991

Mitomycin C as an adjuvant treatment to resected gastric cancer. A 10-year follow-up.

Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up.

Adult↗
PubMed1990

Combination chemotherapy with oral etoposide plus intravenous cyclophosphamide in liver metastases of breast cancer.

Sixteen patients with hepatic metastases of histologically documented breast cancer were treated with etoposide (VP 16-213) and cyclophosphamide. Previously, 6 had shown relapse in the liver after adjuvant chemotherapy, 2 had failed to respond to another chemotherapy combination, and 8 had never undergone chemotherapy. Fifty percent responded to treatment, including 1 complete remission and 7 partial responses. Median survival was 16 months and median duration of response was 13 months. All patients showed alopecia and moderate leukopenia; 13 experienced moderate gastrointestinal toxicity; there was 1 mild case of anemia and 1 case of moderate hemorrhagic cystitis. This study suggests that the combination of VP 16-213 and cyclophosphamide is a well-tolerated and effective treatment in advanced breast cancer patients with liver metastases.

Administration, Oral↗
PubMed1984

Papillary-cystic neoplasm of the pancreas. Report of two cases and review of the literature.

Two cases of papillary-cystic neoplasm of the pancreas are reported in women aged 22 and 23 years. The patient in the first case presented with acute abdominal pain and hemoperitoneum. This form of presentation has not been previously reported. This type of pancreatic tumor is very rare, exclusively affecting young women, and has a good prognosis despite its various histologic features, which suggest a malignant appearance. The authors consider this neoplasm as having an acinar origin because in the cells of one of the patients we observed ultrastructurally the presence of abundant rough endoplasmatic reticulum with formation of annulate lamellae and a few prezymogen granules.

Adult↗
PubMed1983

VP-16 plus cyclophosphamide in the treatment of advanced lung cancer.

Ninety previously untreated patients with histologically documented lung cancer were treated with VP-16 and cyclophosphamide either alone (protocol I) or with methotrexate (protocol II) or Adriamycin (protocol III), with 30 patients in each protocol. The rates of objective response were 57,37, and 27%, respectively, protocol I being significantly better than protocol III (P less than 0.05). Protocol I was significantly less toxic than protocols II(P less than 0.01) and III (P less than 0.001). The overall rate of objective responses was 66% in small cell (SCC) and 22% in non-small cell carcinoma (nSCC). Median survival was 37 weeks in SCC and 21 weeks in nSCC. Median survival of responders both in SCC and in nSCC was significantly longer than in nonresponders. We conclude that VP-16 plus cyclophosphamide is a well tolerated regimen with positive effect in advanced lung cancer. The association of methotrexate or Adriamycin didn't offer any improvement over the basic combination in this study.

Adult↗
PubMed1983

Mitomycin C as an adjuvant in resected gastric cancer.

As a result of their previous experience with mitomycin C at high discontinuous doses in advanced gastric cancer, the authors studied its role as an adjuvant for locally advanced cases after surgical complete resection. Results from 70 evaluable patients are presented. Patients were allocated randomly to receive mitomycin C, 20 mg/m2 I.V. direct once every 6 weeks, four courses, or a placebo. After a follow-up period of 250 weeks, seven patients of treatment arm and 23 controls have already relapsed (p less than 0.001). Toxicity was moderate and controllable by symptomatic measures. The authors consider this investigation a positive contribution in the field of adjuvant therapy of gastric cancer.

Actuarial Analysis↗
PubMed1979

VP 16-213 (VP 16) and cyclophosphamide in the treatment of primitive lung cancer in phase M 1.

Sixty patients suffering from primitive lung cancer in Phase M 1 were included in two successive chemotherapy Protocols, 30 patients to a group. The first of these (an attempt at cellular synchronization by combining VCR-Cyclophosphamide-Prednisone) is used as a historical group as compared to the second. In the second protocol the combination of VP 16.213 (100 mg/m2, po, day X 5 days) and cyclophosphamide (100 mg/m2, ev, day X 5 days) was attempted. The positive results obtained (more than 60% of the responses were above 50%) together with low toxicity was not accompanied by improvement of survival with respect to that observed in international medical literature. On the other hand, the number of cases studied--30 patients--was too low to permit a better evaluation of our results. Despite this fact, it seems appropriate to continue clinical investigation of the VP 16.213-Cyclophosphamide combination in lung cancer.

Adult↗
PubMedDate not supplied

C-erbB-2 oncoprotein in the sera and tissue of patients with breast cancer. Utility in prognosis.

C-erbB-2 serum levels were studied in the sera of 50 healthy subjects, 56 patients with benign breast diseases and 412 patients with breast cancer. Using 15 U/ml as the cut-off, no healthy subjects, patients with benign disease and only 2.4% of patients with no-evidence of disease had serum levels higher than this cut-off point. Abnormal c-erbB-2 levels were found in 9.2% of the patients with locoregional breast carcinoma and in 45.4% of those with advanced disease. C-erbB-2 serum levels in patients with locoregional breast cancer were not related to tumor size or nodal involvement. By contrast, significantly higher c-erbB-2 serum levels were found in ER- or PgR- tumors than in those ER+ or PgR+ tumors, in both locoregional or metastatic tumors. The correlation between serum and tissue levels of C-erbB-2 was studied in the tumors of 161 patients. Significantly higher c-erbB-2 serum levels were found in patients with overexpression in tissue by immunohistochemistry, in both locoregional and advanced disease (p = 0.0001). In patients with C-erbB-2 overexpression in tissue, c-erbB-2 serum levels were related to tumor size and nodes, with higher values in tumors greater than 5 cm or in those with more than 3 nodes involved. When the prognostic value of this oncoprotein was evaluated, patients with abnormally high presurgical c-erbB-2 had a worse prognosis than those patients with normal values, in both node-negative and node-positive patients. Serum concentrations in patients with advanced disease, were related to the site of recurrence with significantly higher values in patients with metastases (mainly in those with liver metastases) than in those with locoregional recurrence. In summary, c-erbB-2 serum level seem to be a useful tumor marker in the prognosis of patients with breast cancer.

Breast Neoplasms↗
PubMedDate not supplied

Tumor markers in response monitoring and prognosis of non-small cell lung cancer: preliminary report.

BACKGROUND: The significance of tumor markers in lung cancer is not well established. PATIENTS AND METHODS: We analyzed level of serum markers as prognostic factor of response and survival in 46 evaluable patients with locally advanced or metastasic non small cell lung cancer. All patients were treated with cisplatin 120 mg/m2 or carboplatin 400 mg/m2 day 1, plus etoposide 80 mg/m2 days 1 to 3. RESULTS: Partial response was obtained in 11 patients (24%), stabilization in 18 and progression in 17. Tumor marker sensitivities were: CEA 37%, CA 125 54.5%, SCC 17.5%, NSE 30.5%, and CYFRA 52%. Higher levels of CEA and NSE correlated with more probability of response (p < 0.001 and p = 0.002). The survival probability of patients with normal pretreatment levels of NSE was significantly better than those with NSE over normal level (15.2 vs 7.2 months) p = 0.02. In patients who achieved partial response, CEA, CA 125 and CYFRA levels decreased significantly with respect to the pretreatment values. CONCLUSIONS: Patients with high CEA and NSE serum level have an increased probability of response than patients with low initial levels; however, patients with high initial level of NSE have poor survival. The decrease in CEA, CA 125 and CYFRA values at the moment of response evaluation could help in response assessment.

Adult↗