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J J Grau

Publications and source records attributed to J J Grau.

At least 19 recordsLinked to original sources

Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.

PURPOSE: We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS: From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS: After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION: Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.

Adenocarcinoma

Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer.

We have used strontium-89 chloride (89Sr) for the palliative treatment of metastatic bone pain. Seventy-six patients (50 males with prostate carcinoma and 26 females with breast cancer) were treated with 148 MBq of 89Sr. Sixteen patients were retreated, receiving two or three doses; the total number of injected doses was consequently 95. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. Three levels of response were considered: good - when there was an increase in the Karnofsky status and a decrease in the pain score (equal to or higher than 4) or analgesic score (equal to or higher than 1); partial - when there was an increase in the Karnofsky status and a decrease in the pain score (2 or 3 points) without significant changes in the analgesic score; no response - if no variation or deterioration in these parameters was observed. In prostate cancer patients, the response was good in 64% of cases and partial in 25%, and there was no response in the remaining 11%. In breast cancer patients, the response was good in 62% of cases and partial in 31%, and there was no response in the remaining 8%. Duration of the response ranged from 3 to 12 months (mean 6 months). In the patients who were retreated the effectiveness was as good as after the first dose of 89Sr. A decrease in the initial leucocyte and platelet counts was observed after the 1st month of treatment, with a gradual partial to complete recovery within 6 months. It is concluded that 89Sr is an effective agent in palliative therapy for metastatic bone pain in patients with prostate or breast carcinoma. If required, retreatment can be administered safely and with the same efficacy as is achieved by the first dose.

Aged

Neoadjuvant and adjuvant chemotherapy in the multidisciplinary treatment of oral cancer stage III or IV.

We performed a retrospective analysis on the effect of initial induction chemotherapy with two courses of cisplatin (each course 120 mg/m2 cisplatin on day 1, then 20 mg/m2 bleomycin (alone) per day for 5 days with 4 weeks between courses) in 75 consecutive patients with advanced cancer of the oral cavity or lip. Further local therapy consisted of surgery or radiation, depending on tumour location. In 18 resected patients adjuvant chemotherapy was added. This consisted of carboplatin, 400 mg/m2 on day 1 then ftorafur alone, 500 mg/m2/day for 30 consecutive days, repeated every month for 4 consecutive months. Among the patients treated in the neoadjuvant setting, complete response was observed in 10 out of 75 patients (13%), and partial response in a further 50 patients (67%) (partial plus complete rate 80%). Of all the patients, 43% in stage III and 26% in stage IV were long-term survivors. Improved survival was observed in surgical patients where adjuvant postoperative chemotherapy was added (P < 0.025). The main toxic effect was vomiting, observed in 71 patients. We noted a low rate of stomatitis (4%) and an important hearing loss (12%). Neoadjuvant and adjuvant cisplatin-based chemotherapy as part of a multidisciplinary approach have a high overall response rate and low toxicity, and should increase survival in cancer of the oral cavity or lip.

Adult

Calcium supplementation and ototoxicity in patients receiving cisplatin.

We have studied the effect on ototoxicity of maintaining serum calcium concentration by calcium gluconate infusion in cancer patients receiving high-dose cisplatin in a randomized study in two groups: 11 patients received calcium gluconate, 4 mg kg-1 i.v. infusion during cisplatin therapy; 11 other patients without any calcium supplementation served as controls. All of them received the first course of chemotherapy, based on cisplatin, 120 mg m2 with a hydration schedule. An audiogram was performed in each patient just before cisplatin and repeated after 1 day and 3 weeks. Mean total calcium concentration in control patients before and after chemotherapy was 2.2 +/- 0.14 (95% confidence interval 1.9-2.5) and 2.0 +/- 0.13 (95% CI 1.7-2.24) mmol 1(-1) respectively (P = 0.0004) and for ionized calcium 1.22 +/- 0.52 (95% CI 0.21-2.23) and 1.11 +/- 0.07 (95% CI 0.97-1.25) mmol 1(-1) respectively (P = 0.0005). Serum magnesium levels were maintained or increased by magnesium supplementation. Although there was no change in serum total or ionized calcium, or serum magnesium in the calcium infusion group, no differences in hearing loss between the groups were observed. High-dose cisplatin chemotherapy for cancer patients induces an acute decrease of serum total calcium and serum ionized calcium and audiometric changes. Maintenance of calcium serum levels by calcium gluconate infusion did not protect against ototoxicity in those patients.

Adolescent

Detection of circulating neoplastic cells by reverse-transcriptase polymerase chain reaction in malignant melanoma: association with clinical stage and prognosis.

PURPOSE: Circulating melanoma cells can be detected in peripheral blood by means of tyrosinase mRNA amplification by reverse-transcriptase polymerase chain reaction (RT-PCR). We conducted a prospective study to evaluate the clinical significance of the presence of circulating neoplastic cells in the blood of patients with malignant melanoma (MM). METHODS: A sensitive RT-PCR assay was used to detect tyrosinase mRNA in the peripheral blood of patients with stages I to IV melanoma. Healthy subjects or patients with other malignancies were used as negative controls. RESULTS: Ninety-one assessable patients were included in the study. There was a statistically significant association between RT-PCR positivity and clinical stage. Circulating melanoma cells were detected in 36% of patients with localized disease (stages I and II), in 45% of patients with regional nodal involvement (stage III), and in 94% of patients with metastatic disease (stage IV) (P < .001). In stage II-III patients who were RT-PCR-positive for mRNA tyrosinase in blood, the recurrence rate and disease-free survival were significantly worse than patients who were RT-PCR-negative. In multivariate analysis, RT-PCR was an independent prognostic factor for recurrence in patients with nonmetastatic disease (P = .002). CONCLUSION: The detection of circulating melanoma cells in peripheral blood by RT-PCR correlated with the clinical stage of patients with melanoma and was an independent prognostic factor for recurrence. Further studies are warranted to better assess the significance of this test in the evaluation of prognosis, early detection of relapse, and in monitoring the effectiveness of systemic therapy.

Adult

Chronic oral etoposide in advanced breast cancer.

Chronic oral etoposide has shown activity in some metastatic refractory tumors. To test its activity in previously treated metastatic breast cancer patients, we started a study in 18 consecutive patients given etoposide orally at 50 mg/m2 daily for 21 days. A partial response was observed in 4 of 18 patients (22%); of the responding patients, 3 had visceral metastases and 1 had multiple bone metastases. Leukopenia of grade 3 or 4 was the main hematological toxic effect (23% of patients) and alopecia was the most important nonhematological toxicity. Chronic oral etoposide shows some activity in pretreated patients with metastatic breast cancer, with tolerance being good and toxicity, acceptable. Further studies of this drug given as first-line chemotherapy or in combination with other drugs can establish all its potential activity in this cancer.

Administration, Oral

Age and clinical characteristics of 1433 patients with lung cancer.

A review has been conducted of 1433 patients treated by the Lung Cancer Unit of our hospital to assess the association of age with clinical characteristics of patients with lung cancer. The factors evaluated were tobacco, stage of disease, treatment and survival of patients treated surgically. A comparison was made of patients aged 65 or less with those over 65. There was a similar prevalence of smokers in both age groups. The stage of disease at time of diagnosis was similar (33% of the patients aged 65 or less were Stage I or II versus 37% of the older patients). The distribution by histological type showed significant differences (p < 0.05) with a higher percentage of squamous carcinoma in the younger group (54% versus 44%). Surgery was performed in 30% of the patients aged 65 years or less but only in 19% of the older cases (p < 0.05). Among those patients treated surgically there was no difference in the survival of younger and older patients.

Aged

Carboplatin plus ftorafur as a palliative treatment in locally advanced cancer of the oral cavity and lip.

Forty consecutive patients with local advanced cancer of the oral cavity and lip, heavily pretreated, were palliated with two courses of carboplatin, 400 mg/m2 intravenously once a month plus ftorafur, 500 mg/m2 daily per os for 30 days. Previous treatment consisted of surgery (17 patients), radiation therapy (23 patients), and chemotherapy with cisplatin plus bleomycin (15 patients). The main sites of primary tumor were the tongue (12 patients), hard palate (6 patients), retromolar area (6 patients), tonsils (6 patients), perioral skin and lip (5 patients), and floor of the mouth (5 patients). Complete response was observed in 3 patients, and partial response in 7. Symptomatic improvement was observed in 56% of the cases. Median duration of response was 9 months. Median survival was 7 months. The main toxic effects were nausea (39 cases), vomiting (35 cases), and thrombocytopenia (4 cases). We conclude that carboplatin plus ftorafur has a role as palliative chemotherapy in cancer of the oral cavity and lip in heavily pretreated patients when local therapies are not suitable.

Adult

Use of CA 19-9 in the early detection of recurrences in colorectal cancer: comparison with CEA.

The serum levels of CA 19-9 were determined in the follow-up of 370 patients with colorectal cancer and compared with CEA. An increase in CA 19-9 preceded clinical diagnosis of recurrence in 25% of 72 patients. The mean time between the rise in CA 19-9 and clinical diagnosis of relapse was 3.7 months (median 3). Sensitivity of CA 19-9 in the early diagnosis of recurrence was much lower than that obtained for CEA (75%). Only 1 patient had elevated CA 19-9 levels and normal CEA.

Antigens, Tumor-Associated, Carbohydrate

TAG-72, CA 19.9 and CEA as tumor markers in gastric cancer.

Serum levels of CEA, CA 19.9 and TAG-72 were measured in 79 patients with active gastric cancer, 47 with treated gastric cancer and no clinical evidence of the disease and 33 with benign gastric disease. In the patients with active gastric cancer TAG-72 was increased in 47%, CA 19.9 in 46% and CEA in 33%. The sensitivity of these markers was related to the stage of the disease, although upon comparison of stages I-II and III-IV significant difference was observed only for TAG-72. The combined use of two of the markers increased the sensitivity compared with the use of only one. The results suggest that the combination of TAG-72 and CA 19.9 may be useful in the post surgical management of patients with gastric cancer.

Antigens, Neoplasm

Positive results of adjuvant mitomycin-C in resected gastric cancer: a randomised trial on 134 patients.

In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a randomised trial on 134 patients in two arms: a control one with no further treatment after surgery versus a treatment arm given mitomycin-C (MMC), 20 mg/m2 intravenously one day every 6 weeks for four courses, starting before the sixth week after surgery. The median follow-up was 105 months. In the control arm, 49 out of 66 patients died due to recurrence, versus 40 out of 68 patients in treatment arm. Actuarial survival curve was statistically significant (P < 0.025) in favour of the treatment group. Liver metastases were lower in adjuvant group than in the control group (8/68 versus 19/66). Toxicity was mild. Main toxic effects were thrombocytopenia, leukopenia, nausea and vomiting. A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed. In that particular case MMC was given after surgery. We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery, improves survival rate in gastric cancer resected patients.

Adult

Chronic oral etoposide in non-small cell lung carcinoma.

25 consecutive inoperable or extended non-small cell lung cancer (NSCLC) patients (19 non-chemotherapy pretreated, 6 non-heavily pretreated) were given oral etoposide, 50 mg/m2/day for 21 successive days, every 4 weeks. 5 partial responses (PR), 9 disease stabilizations were achieved; the overall response rate of 20% (95% confidence interval, 4% to 36%) or 26% in non-pretreated patients. Median survival and PR duration probabilities were 6.7 months and 6.3 months, respectively. Alopecia excepted (96% of patients), non-haematological toxicity was mild. Haematological toxicity WHO grade II+III mainly consisted of leukopenia (28%).

Administration, Oral

Cancer diagnosis disclosure in a Spanish hospital.

At the Clinic Hospital in Barcelona, Spain, 167 cancer patients and 380 hospital health care workers were interviewed about cancer diagnosis disclosure. Only 25 patients (15%) were correctly informed of their diagnoses. Breast cancer patients were significantly more often informed than patients with other malignancies (p less than 0.05). Two hundred seventy-two of 380 hospital health workers interviewed (71%, p = 0.00) would want to know their own diagnoses should they suffer from cancer in the future, but only 19% (p = 0.00) would want such a diagnosis revealed to their similarly afflicted relatives. This information model, based on cancer taboo, is largely preferred by these healthy people and is followed by doctors, patients and family members. To inform our patients better, the mandatory uniform disclosure of the true diagnosis is not likely to be constructive at present. In our opinion a pragmatic approach is more realistic and humane. Nevertheless, we must hope that more modern cancer education will lead to the gradual elimination of this taboo in our society.

Aged

Phase II trial of carboplatin and etoposide activity in pretreated breast cancer patients.

Twenty-seven metastatic breast adenocarcinoma patients, pretreated with standard hormonotherapy or chemotherapy, received carboplatin 100 mg/m2/day x 3 intravenously (i.v.) plus etoposide 100 mg/m2/d x 3 i.v. repeated at 4-week intervals. There were five partial responses (18.5%), two minor responses, and 12 disease stabilizations. The dominant metastatic disease sites were soft tissue in three partially responding patients and visceral metastases in the two remaining responders. The median duration of response and time to progression were, respectively, 10 and 26 weeks. Major toxicity was myelosuppression with 85% of patients developing leukopenia; 48%, anemia; and 30%, thrombocytopenia. Carboplatin plus etoposide has shown antitumor activity in our group of pretreated patients. Based on the same schedule, a first-line carboplatin plus etoposide Phase II trial has been started.

Adenocarcinoma

Prognostic value of CA 19.9 levels in colorectal cancer.

Pretreatment serum levels of carbohydrate antigen 19.9 (CA 19.9) and carcinoembryonic antigen were measured in 293 patients with colorectal cancer. Carbohydrate antigen 19.9 was above the cut-off limit of 37 U/mL in 35% of patients. Carbohydrate antigen 19.9 sensitivity was related to tumor stage. Carcinoembryonic antigen was above the cut-off level of 3.5 ng/mL in 61% of patients, and the simultaneous use of two markers increased sensitivity to 66%. The main use of pretreatment levels of CA 19.9 in locoregional cancer is in prognosis. Carbohydrate antigen 19.9 provided more prognostic information than that obtained by conventional staging methods. In patients with Dukes' C tumors, additional information was obtained for allocation of these patients into groups at low or high risk of recurrence. Prognostic significance of carcinoembryonic antigen was not independent of Dukes' classification.

Antigens, Tumor-Associated, Carbohydrate

Intracavitary oxytetracycline in malignant pericardial tamponade.

We started a treatment trial for malignant pericardial tamponade with intracavitary oxytetracycline, 500-1,000 mg/day, administered via an indwelling pericardial cannula after extraction of as much pericardial fluid as possible. This procedure was repeated every 24 h for 6 consecutive days or until no more fluid could be drained. Eleven consecutive patients were entered in the study. The responses were obtained by clinical examination, chest roentgenogram and echocardiogram, prior to and after treatment. The primary cancer was located in the breast in 7 patients, in the stomach in 2 patients, and in the lung in 2 patients. In all cases, systemic chemotherapy or hormonal therapy was started after the pericardial tamponade was cured. The mean tetracycline dose per patient was 3,000 mg (range 1,500-6,000). All patients responded to the treatment with rapidly improving symptoms. Response persisted during a median of 9 months coinciding roughly with the median survival because all patients died because of progression of the neoplasm at sites other than the pericardium with no evidence of pericardial relapse. The main concomitant effects were mild local pain during tetracycline instillation in 4 patients, and transient fever (less than 39 degrees C) in 3. These data suggest that intracavitary oxytetracycline is perhaps less toxic and similar by successful as tetracycline hydrochloride in malignant pericardial tamponade.

Adult

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