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Biomedical subjects

C Theodore

Publications and source records attributed to C Theodore.

At least 19 recordsLinked to original sources
PubMed1996

Cisplatin-based chemotherapy after retroperitoneal lymph node dissection in patients with pathological stage II nonseminomatous germ cell tumors.

In order to assess the results of cisplatin-based chemotherapy after primary lymph node dissection in patients with pathological stage II nonseminomatous germ cell tumors of the testis, we retrospectively reviewed the long-term outcome of 44 patients who received adjuvant chemotherapy at Institut Gustave Roussy over a 7-year period. Two chemotherapy regimens were sequentially delivered. Twenty-three patients were treated with vinblastine, cyclophosphamide, bleomycin, actinomycin D, and cisplatin (mVAB-6, four cycles), while 21 patients received a combination of etoposide and cisplatin (EP, four cycles). After a median follow-up of 6 years, all patients remain free from progression. The long-term toxicity included retrograde ejaculation in eight patients and severe ototoxicity in two patients. We conclude that four cycles of cisplatin-based chemotherapy for pathological stage II testicular cancer resulted in a 100% cure rate with minimal toxicity.

Adolescent↗
PubMed1996

Primary chemotherapy in patients with nonseminomatous germ cell tumors of the testis and biological disease only after orchiectomy.

PURPOSE: We assessed the efficacy of primary chemotherapy in patients with nonseminomatous germ cell tumors of the testis and elevated serum tumor markers as the only evidence of disease after orchiectomy. MATERIALS AND METHODS: We analyzed the outcome of 20 patients with biological disease only who received cisplatin-based (16) or carboplatin-based (4) chemotherapy as primary treatment following orchiectomy. RESULTS: Serum tumor markers returned to normal levels in all 20 patients. One patient required subsequent surgery for recurrent retroperitoneal mature teratoma. Two patients experienced a relapse with active disease, 1 of whom died of progressive germ cell tumor. Of the patients 19 remained free of disease 18 to 116 months after the end of treatment. CONCLUSIONS: Since results with primary retroperitoneal lymph node dissection suggest that elevated serum tumor markers usually reflect systemic metastases rather than retroperitoneal disease, primary chemotherapy seems to be the most appropriate strategy to consider in patients with biological disease only following orchiectomy.

Adolescent↗
PubMed1995

The p53 and mdm-2 genes in human testicular germ-cell tumors.

Mutations in the p53 gene are common in many cancers. They have been documented to occur in about 55% of all cancers of 51 different cell and tissue types. These mutations are accompanied by overexpression of the p53 protein in the nucleus of the cell, and this protein has lost its tumor suppressor function. In this study, 25 testicular germ-cell (TGC) tumors were tested for p53 mutations and the level of p53 protein expression. While 67% of the tumors overproduced the p53 protein in the nucleus of 10-60% of their cells, in all cases the DNA sequence of exons 4-9 of the p53 gene was wild type. In this tumor type, there was apparently no selection pressure for p53 mutations. The mdm-2 gene residues on chromosome 12 (12q13-q14), a chromosome often altered in TGC tumors. mdm-2 gene amplification (2.5- to 10-fold) was detected in three (12%) of these TGC tumors. These three tumors, and eight additional TGC tumors, overexpressed mdm-2 mRNA. There was a good correlation between overexpression of p53 protein and overexpression of mdm-2 mRNA (P = 0.01). This may well result from the fact that the level of mdm-2 mRNA is regulated by the p53 level. These studies demonstrate that TGC tumors fail to be selected for p53 mutations but nonetheless frequently expressed high levels of wild-type p53 protein in the cell nucleus. Perhaps this produces the excellent response to radiation and chemotherapy of these tumors, which generally have a good prognosis. Wild-type p53 may mediate apoptosis in these cells in response to the DNA damage.

Base Sequence↗
PubMed1995

Phase II trial of ifosfamide, fluorouracil, and folinic acid (FIFO regimen) in relapsed and refractory urothelial cancer.

There is no known effective salvage chemotherapy for patients with refractory or relapsed urothelial tumors after methotrexate/cisplatin-based regimen. We report the results of a phase II trial with the FIFO regimen that includes from day 1 to 5: fluorouracil 350 mg/m2, folinic acid 20 mg/m2, and ifosfamide 1000 mg/m2, Q4W. Fifteen patients with metastatic measurable urothelial cancer were enrolled in this trial. Previous therapy included M-VAC regimen in 11 patients, CMV regimen in 3 patients, and both regimens in 1 patient. Thirty-one courses were delivered. Toxicity was moderate, including encephalopathy grade 2 in 2 patients and hematological toxicity grade 3 in 2 others. However, an early death occurred on day 1 in a patient who progressed rapidly and died from hepatic insufficiency after initial encephalopathy. No objective response was seen. Twelve patients progressed during FIFO therapy and 3 patients experienced a stable disease. Despite almost encouraging results of fluorouracil and ifosfamide in the literature, their combination according to our schedule is not active in urothelial cancer.

Adrenal Gland Neoplasms↗
PubMed1995

[Desmoplastic small round cell tumors in adults: a new entity].

Desmoplastic small round cell tumor is a recently recognized clinicopathologic entity with distinctive morphologic and immunohistochemical features. Moreover, specific cytogenetic and molecular characteristics have been described. We report here five new adult cases. The median age was 22 years. The clinical presentation was intra-abdominal in four patients and para-testicular in one patient. In patients with intra-abdominal disease, the initial surgery consisted of suboptimal debulking in three patients and only biopsies in the fourth. The patient with para-testicular tumor underwent an orchiectomy. Chemotherapy including cisplatin, etoposide, cyclophosphamide and doxorubicin or epirubicin (PAVEP/PEVEP regimen) was delivered after initial surgery in patients with intra-abdominal presentation or at relapse in the patient with para-testicular tumor. Only one persistent complete response was obtained and no salvage treatment was active in the other patients who died of progressive disease. A review of the literature concerning the clinicopathologic, cytogenetic and molecular features of this new entity is exposed.

Abdominal Neoplasms↗
PubMed1992

Phase II trial of 7-day continuous 5-fluorouracil infusion in the treatment of advanced colorectal carcinoma.

Thirty-eight patients with advanced colorectal adenocarcinoma were entered on a phase II trial of 5-fluorouracil (5-FU) in continuous infusion, using a portable pump. Half of the patients had been pretreated (n = 19) and 16 of them had received intravenous bolus 5-FU alone or in combination. At the first cycle patients received continuous intravenous 5-FU at the dose of 650 mg/m2 per day for 7 consecutive days. Doses were escalated during the following cycles and adjusted according to the toxicities encountered in the previous cycle. Treatment was repeated every 3 weeks. A mean dose of 750 mg/m2/day (500-1,000) was administered for a mean number of 10 (1-25) cycles. We observed 1 complete response, 7 partial responses for a response rate of 21 +/- 13% (CI95%), 16 had stable disease (42%) and 14 a progression (37%). In 2 patients subsequently the residual tumors could be excised after chemotherapy. Median survival was 13.5 months. Toxicity was: grade 2 leukopenia in 1 patient (3%), mucositis grade 2-4 in 11 patients (29%), diarrhea grade 2-3 in 7 patients (18%), and hand and foot syndrome in 12 patients (31%). There was a correlation between the mean dose administered and the responses. However no clear correlation was found between toxicity and tumoral response for the first two cycles. These results confirm the limited efficacy of continuous intravenous 5-FU and its good tolerance in ambulatory patients.

Actuarial Analysis↗
PubMed1991

Metastatic carcinoid and islet cell tumours of the pancreas: a phase II trial of the efficacy of combination chemotherapy with 5-fluorouracil, doxorubicin and cisplatin.

A phase II trial of chemotherapy in carcinoid and islet cell pancreatic tumours has been conducted with the FAP protocol: 5-fluorouracil 400 mg/m2 per day (5-FU) for 3 days, 50 mg/m2 doxorubicin on day 2, and 90 mg/m2 cisplatin on day 2, repeated every 4 weeks. 24 patients, 20 non-pretreated and 4 pretreated, were included. For non-pretreated patients we observed 1 complete response and 2 partial responses. The response rate was 15% (95% confidence interval 0-31%). No response was observed in the pretreated patients. The toxicity was mainly digestive and haematological with 7 patients experiencing vomiting grade 3 and 3 patients with leucopenia grade 3. We conclude that the FAP protocol is of poor efficiency in endocrine tumours.

Adenoma, Islet Cell↗
PubMed1991

Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer.

Between April 1984 and May 1985, 17 heavily pretreated patients with relapsing or refractory germ cell tumours were treated with cisplatin 40 mg/m2/day, days 1-5; etoposide 350 mg/m2/day, days 1-5; cyclophosphamide 1600 mg/m2/day, days 2-5 and autologous bone marrow transplantation on day 8 as consolidation of conventional salvage chemotherapy. None of the 11 refractory patients and 4 of the 6 responders to prior salvage treatment are long-term survivors at 68, 72, 74 and 74 months. Mean aplasia duration was 17 days and there were 7 documented episodes of septicaemia in 17 febrile patients. 1 patient died of treatment. Among the 4 survivors, 2 patients have a sustained grade II invalidating neuropathy. We conclude that this regimen is not recommended as salvage therapy in refractory patients but may be a useful consolidation treatment in patients responding to conventional salvage chemotherapy.

Adolescent↗
PubMed1990

Phase II trial of ifosfamide in the treatment of metastatic hormone-refractory patients with prostatic cancer.

Cyclophosphamide has been considered one of the reference drugs of chemotherapy in randomized trials in hormone-refractory prostate cancer by the National Prostatic Cancer Project (NPCP). Ifosfamide, another oxazaphosphorine agent, and an analog of cyclophosphamide, appears to be more active and less toxic in a broad spectrum of tumors. Fifteen patients with metastatic hormone-refractory prostate cancer were treated with continuous infusion of ifosfamide 2 g/m2 per day for 2 days, together with the uroepithelial protective agent Mesna 2.4 g/m2 per day for 2 days, both to be repeated every 3 weeks. All patients have failed on previous hormonal therapy and 7 patients had received previous chemotherapy. The median age was 66 years. Fourteen patients were evaluable; none of whom achieved an objective response. Four patients were stabilized and 10 had disease progression while on chemotherapy. Major toxicity included 2 reversible encephalopathy, 3 grade I reversible renal toxicity, and 1 hemorrhagic cystitis. We concluded that ifosfamide given in this schedule in this group of patients is not an active agent in prostate cancer.

Aged↗
PubMed1990

[Primitive digestive localizations of malignant non-Hodgkin's lymphoma. Prognostic factors of locally advanced disease: stage II. Report of 67 cases].

Sixty-seven patients with non-Hodgkin's lymphoma of the digestive tract with locally advanced disease (stage II) were analyzed to determine the main factors influencing survival. There were 19 patients with stage II E1 and 48 with stage II E2 disease (Musshoff classification). According to the Kiel classification, 46 percent were low grade, 46 percent were high grade, and 8 percent were unclassified. The principal sites involved included the stomach: 11 cases, small intestine: 21 cases, colon: 12 cases, and mesentery: 11 cases. Lymphoma was unique in 45 cases (67 percent). Treatment consisted of laparotomy in 61 of 67 cases: partial resection was achieved in 21 cases, complete resection in 27 cases, and exploration only in 13 cases. Chemotherapy, according to histopathological subtypes, was employed in 90 percent of cases. Radiation therapy was applied in 25 patients (37 percent), essentially when there was residual disease after surgery (17 patients). Therapeutic indications were dependent on histological subtype, extension, and the therapy regimen in use at the time of treatment. Five patients were treated by surgery only, 2 by surgery and radiation therapy, 37 by surgery followed by chemotherapy, and 23 by all three treatment modalities. Overall survival was 62 percent at 5 years. Univariate analysis showed that 5-year survival rates were not influenced by sex, age, histopathological subtype (low grade: 69 percent; high grade: 59 percent; NS) or local extension (stage II E1: 76 percent vs stage II E2: 59 percent; NS). In contrast, complete surgical excision (p = 0.06) and radiation therapy in case of local residual disease (p = 0.02) seemed to improve survival. The main prognostic factor was the achievement of a complete therapeutic response (CR) (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

[Chemotherapeutic intensification in germ cell tumors].

Chemotherapy has dramatically improved the prognosis of non-seminomatous germ cell tumors (NSGCT). However, some patients relapse and others are refractory to first line chemotherapy. We studied a salvage chemotherapeutic regimen with etoposide 75 gm/m2/day, and cisplatin 40 mg/m2/day, days 1-5 and Ifosfamide 3 g/m2/day, days 1 and 2 (VIhP regimen) in 32 patients. We observed 8 complete remissions with 4 long-term NED patients. Hematological, neurological and renal complications were frequent. In 16 other cases, a protocol using high dose chemotherapy, followed by autologous bone marrow rescue was studied. We observed 8 complete remissions with 4 long-term NED patients. These observations support a dose/effect relationship. A French randomized trial testing high dose chemotherapy, followed in some cases by an autologous marrow graft in poor risk advanced NSGCT, has recently been activated.

Adolescent↗
PubMed1989

Treatment of high-risk gestational trophoblastic disease with chemotherapy combinations containing cisplatin and etoposide.

The authors have treated 22 patients with high-risk gestational trophoblastic disease (GTD) by cisplatin-etoposide-containing combinations. Sixteen patients were treated with dactinomycin, platinum, and etoposide combination (APE regimen) and six patients had platinum and etoposide combination (PE regimen). Fourteen patients were treated for resistant or relapsing GTD after first-line therapy, and eight patients initially. All 22 patients were high risk according to the World Health Organization prognostic score values. Sustained complete remission was achieved in 19 patients (86%). All eight patients who received treatment as initial therapy were cured (100%) whereas only 11 patients were cured among the 14 patients who failed prior chemotherapy (78%). Hematologic and renal toxicities were limited and no treatment-related deaths occurred in this group of patients. Cisplatin and etoposide could be more widely used in chemotherapeutic combinations for high-risk gestational trophoblastic disease.

Adult↗
PubMed1989

Cisplatin, vinblastine, and bleomycin combination in the treatment of resistant high-risk gestational trophoblastic tumors.

Eight patients with high-risk gestational trophoblastic tumors (GTT) resistant to multiagent chemotherapy were treated with the combination of cisplatin, vinblastine, and bleomycin (PVB). All patients had a metastatic disease including three patients with two metastatic sites and two patients with brain metastases. Four patients achieved complete remission (CR) with the PVB regimen (50%). Three additional patients had partial remission (PR) of whom two were converted into CR by surgery of resistant residual lesions. One patient relapsed and the remaining five patients in CR were cured (62%). A multimodal approach was necessary in most patients as five of them had hysterectomy and two patients had a whole-brain irradiation. Toxicity was mild with no treatment related deaths.

Adult↗
PubMed1989

Prognostic factors in primary gastrointestinal non-Hodgkin's lymphoma. A multivariate analysis, report of 106 cases, and review of the literature.

The authors have reviewed 106 cases of primary gastrointestinal non-Hodgkin's lymphoma (GI-NHL) treated at the Institut Gustave-Roussy (IGR), France, between 1975 and 1986. The occurrence was 55 in the stomach, 26 in the small intestine, ten ileocecal, seven in the large intestine, and eight patients had multiple involvement. Patients were clinically staged according to the Ann Arbor staging system using the modification of Musshoff for Stage IIE. All histologic material of the 106 patients were reviewed and graded according to the Working Formulation (WF) and the Kiel classifications. Most patients received combination chemotherapy as part or all of their primary treatment program (95 patients, 90%). Seventy five patients (71%) had a multimodality treatment. The overall 5-year survival rate was 60%. Sixteen variables were tested by univariate analyses for prognostic influence on survival. Of these, only clinical stage (P less than 0.001), the achievement of initial complete remission (CR) (P less than 0.001), erythrocyte sedimentation rate (ESR) (P = 0.01), mesenteric involvement (P = 0.03), and serosal infiltration (P = 0.05) were significant prognostic factors. Important variables were tested by a multivariate analysis using the Cox model taking into account different treatment modalities. Only three variables entered the regression analysis at a significant level: clinical stage (P = 0.02), surgical resection (P = 0.03), and histologic grade (Kiel) (P = 0.04). When the achievement of initial CR was introduced into the model, it was the most significant variable (P less than 0.001) whereas all other variables became nonsignificant except for the histologic grade (Kiel) (P = 0.004). Based on results of the multivariate analyses we propose two prognostic classifications of patients: one at the initial evaluation depending on clinical stage, surgical resectability, and histologic grade (Kiel); the other at the end of primary treatment depending on the achievement or not of CR and the histologic grade.

Adolescent↗
PubMed1989

Phase II trial of combination chemotherapy with dacarbazine, cyclophosphamide, cisplatin, doxorubicin, and vindesine (DECAV) in advanced renal cell cancer.

Eighteen patients with advanced renal cell cancer were evaluated for objective response to a combination chemotherapy regimen twenty-eight-day (d) cycles, with dacarbazine (200 mg/sq m/d, d1,2,3); cyclophosphamide (400 mg/sq m/d, d1); cisplatin (100 mg/sq m/d, d1); doxorubicin (50 mg/sq m/d, d1); vindesine (1.5 mg/sq m/d, d1,2) (DECAV). One response in 16 patients was observed (6.25%; 95% confidence limits are 0-30%). No major toxicity occurred. An important point is that the only complete remission was observed in a patient with sarcomatoid cell renal cancer. At this dose with this schedule this combination regimen appears to have no activity in renal cell carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗