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Biomedical subjects

C Theodore

Publications and source records attributed to C Theodore.

At least 19 recordsLinked to original sources
PubMed2006

A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen.

A multicentre phase II trial to determine the efficacy of vinflunine as second-line therapy in patients with advanced transitional cell carcinoma (TCC) of the bladder; secondary objectives were to assess duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients had tumours that failed or progressed after first-line platinum-containing regimens for advanced or metastatic disease, or had progressive disease after platinum-containing chemotherapy given with adjuvant or neoadjuvant intent. Response and adverse events were assessed according to WHO criteria and NCI-CTC (version 2), respectively. Out of 51 patients treated with 320 mg m(-2) of vinflunine, nine patients responded to the therapy yielding an overall response rate of 18% (95% CI: 8.4-30.9%), and 67% (95%CI: 52.1-79.3%) achieved disease control (PR+SD). Of note, responses were seen in patients with relatively poor prognostic factors such as a short (<12 months) interval from prior platinum therapy (19%, including an 11% response rate in those progressing <3 months after platinum treatment), prior treatment for metastatic disease (24%), prior treatment with vinca alkaloids (14%) and visceral involvement (20%). The median duration of response was 9.1 months (95% CI: 4.2-15.0) and the median PFS was 3.0 months (95% CI: 2.4-3.8). The median OS was 6.6 months (95% CI: 4.8-7.6). The main haematological toxicity was grade 3-4 neutropenia, observed in 67% of patients (42% of cycles). Febrile neutropenia was observed in five patients (10%) and among them two were fatal. Constipation was frequently observed (but was manageable and noncumulative) and was grade 3-4 in only 8% of patients. The incidence of grade 3 nausea and vomiting was very low (4 and 6% of patients, respectively). Neither grade 3-4 sensory neuropathy nor severe venous irritation was observed. Moreover, and of importance in this particular study population, no grade 3-4 renal function impairment was observed. Vinflunine is an active agent for the treatment of platinum-pretreated bladder cancer, and these results warrant further investigation in phase III trials, either as monotherapy or in combination with other agents as treatment of advanced/metastatic TCC of the bladder.

Adult↗
PubMed2006

A phase II monocentric study of oxaliplatin in combination with gemcitabine (GEMOX) in patients with advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract.

BACKGROUND: The aim of the study was to evaluate the activity and the safety of the gemcitabine-oxaliplatin (GEMOX) combination as first-line treatment in advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract. MATERIALS AND METHODS: Patients with metastatic or unresectable TCC, PS < or =2, creatinine < or =1.5 upper limit of normal range (UNL) and measurable disease according to RECIST criteria were treated with a combination of gemcitabine (1500 mg/m(2)) followed by oxaliplatin (85 mg/m(2)) on day 1 and 15 of a 28-day cycle. RESULTS: A total of 123 cycles were administered to 30 patients (median 4, range 1-8). Three complete responses (CR) and 11 partial responses (PR) were observed. Overall response rate (ORR) was 47% (95% CI 28% to 66%). Median overall survival (OS) was 15 months (95% CI 8-31). Grade 3 and 4 neutropenia were reported in three and one patient, respectively; grade 3 anaemia in three patients; grade 3 and 4 thrombocytopenia in two and one patient, respectively; grade 1, 2 and 3 peripheral neuropathy in 14, 11 and two patients, respectively; grade 2 and 3 fatigue in 13 and seven patients respectively. CONCLUSIONS: The GEMOX combination is active in advanced/metastatic TCC with minimal toxicity and needs to be evaluated in a selected population of unfit patients and compared with other non-cisplatin-containing regimens.

Aged↗
PubMed2005

Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours.

EORTC protocol 30924 is an international randomized trial reporting a 7.3 year update of a 2 weekly regimen of high-dose intensity chemotherapy with M-VAC plus granulocyte colony stimulating factor (HD-M-VAC) compared to classic M-VAC in advanced transitional cell carcinoma (TCC). Two hundred and sixty three untreated patients with bidimensionally measurable TCC were included. In an intention to treat analysis, there were 28 complete responses (CR) (21%) and 55 partial responses (PR) (41%), for an overall response rate (RR) of 64% on the HD-M-VAC arm. On M-VAC, there were 12 CR (9%) and 53 PR (41%), for an overall RR of 50% . The P-value for the difference in CR was 0.009; and for RR, was 0.06. After a median follow-up of 7.3 years, 24.6% are alive on the HD-M-VAC arm vs. 13.2% on the M-VAC arm. Median progression-free survival was better with HD-MVAC (9.5 months) vs. M-VAC (8.1 months). The mortality hazard ratio (HR) was 0.76. The 2-year survival rate for HD-M-VAC was 36.7% vs. 26.2% for M-VAC. At 5 years, the survival rate was 21.8% in the HD-M-VAC vs. 13.5%. Median survival was 15.1 months on HD-MVAC and 14.9 months on M-VAC. There was one death from toxicity in each arm; and more patients died to malignant disease in the M-VAC arm (76%) than in the HD-M-VAC arm (64.9%). With longer follow-up initial results have been confirmed, and shows that HD-M-VAC produces a borderline statistically significant relative reduction in the risk of progression and death compared to M-VAC.

Adult↗
PubMed2005

A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours.

BACKGROUND: Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients. This phase III randomised trial compares conventional salvage to high-dose-intensification chemotherapy. PATIENTS AND METHODS: Between February 1994 and September 2001, 280 patients from 43 institutions in 11 countries, were randomly assigned to receive either four cycles of cisplatin, ifosfamide and etoposide (or vinblastine) (arm A), or three such cycles followed by high-dose carboplatin, etoposide and cyclophosphamide (CarboPEC) with haematopoietic stem cell support (arm B). RESULTS: Similar complete and partial response rates were observed in both treatment arms (56%; 95% CI 50% to 62%). There were 3% and 7% toxic deaths in arms A and B, respectively. No significant improvements with CarboPEC were observed in either 3-year event-free survival (35% versus 42%, P=0.16) or overall survival (53%; 95% CI 46% to 59%). Complete responders with CarboPEC had a significant improvement in disease-free survival (55% versus 75% at 3 years, P <0.04). CONCLUSIONS: The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes. These results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.

Adolescent↗
PubMed2005

Phase III trial of satraplatin, an oral platinum plus prednisone vs. prednisone alone in patients with hormone-refractory prostate cancer.

Satraplatin is a novel oral platinum (IV) complex that shows activity against hormone-refractory prostate cancer (HRPC) in cisplatin-resistant human tumor lines in phase I and phase II trials. A randomized multicenter phase III trial with a target sample size of 380 patients was initiated in men with HRPC. After 50 randomized patients, the trial was closed to further accrual by the sponsoring company. An ad hoc analysis of all available data is reported here. Eligibility criteria included pathological proof of prostate cancer, documented progression despite prior hormonal manipulation, WHO PS 0-2, and no daily intake of narcotic analgesics. Patients were randomized between satraplatin 100 mg/m(2) for 5 days plus prednisone 10 mg orally BID or prednisone alone. Compliance was excellent. 48/50 patients have progressed and 42 have died, mostly due to prostate cancer. Median overall survival was 14.9 months (95% CI: 13.7-28.4) on the satraplatin plus prednisone arm and 11.9 months (95% CI: 8.4-23.1) on prednisone alone (hazard ratio, HR = 0.84, 95% CI: 0.46-1.55). A >50% decrease in prostrate specific antigen (PSA) was seen in 9/27 (33.3%) in the satraplatin plus prednisone arm vs. 2/23 (8.7%) on the prednisone alone arm. Progression-free survival was 5.2 months (95% CI: 2.8-13.7) on the satraplatin plus prednisone arm as compared to 2.5 months (95% CI: 2.1- 4.7) on the prednisone alone arm (HR = 0.50, 95% CI: 0.28-0.92). This difference is statistically significant (p = 0.023). Toxicity was generally minimal in both arms. This randomized comparison of a combination of satraplatin and prednisone versus prednisone alone supports the antitumor activity of the combination. Its role in the treatment of HPRC remains to be elucidated in an appropriate phase III setting.

Adenocarcinoma↗
PubMed2005

Multicentre EORTC study 16997: feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers.

In this study, the feasibility and activity of combined chemotherapy of the farnesyl transferase inhibitor SCH66336 and gemcitabine was evaluated. This therapy was used as second-line treatment in patients with advanced urothelial tract cancer and the influence of SCH66336 exposure on the pharmacokinetics of gemcitabine was also determined. Patients who had received one previous chemotherapy regime for advanced urothelial cancer were treated with a combination of SCH66336 (150 mg in the morning and 100 mg in the evening) and Gemcitabine (1000 mg/m2 on day 1, 8 and 15 per 28-day cycle). Dosages of gemcitabine and its metabolite dFdU were performed on day one of cycle 1 before exposure to SCH66336 and day one of cycle 2. A total of 152 cycles were administered in 33 patients (median 3, range: 1-15). No patients had severe hematological toxicity, defined as Grade 4 thrombocytopenia or febrile neutropenia. Nine partial responses and one complete response were achieved in 31 assessable patients and corresponded to an overall response rate of 32.3% [95% CI:17%-51%]. There was no influence of exposure to SCH66336 on the level of gemcitabine or dFdU in 11 assessable patients. In conclusion, a combination of SCH66336 and gemcitabine is feasible in terms of toxicity and active as second-line treatment in patients with advanced urothelial tract cancer. SCH66336 had no effect on the pharmacokinetics of gemcitabine. Randomised trials should be undertaken to clarify the role of SCH66336 in combination with gemcitabine in cancer treatment.

Adult↗
PubMed2003

Acute respiratory distress syndrome after chemotherapy for lung metastases from non-seminomatous germ-cell tumors.

GOALS: To describe an acute respiratory distress syndrome (ARDS) occurring after chemotherapy for non-seminomatous germ-cell tumors (NSGCT) with diffuse lung metastases, we conducted a retrospective study in a 15-bed intensive care unit (ICU) in a comprehensive cancer center. PATIENTS AND METHODS: During a 10-year period, 16 consecutive patients with diffuse lung metastases from a NSGCT were admitted to the ICU for respiratory distress and high-risk chemotherapy. MAIN RESULTS: Nine patients developed acute respiratory failure requiring mechanical ventilation (MV) within 3 days of the initiation of chemotherapy, while the respiratory status of the seven other patients improved. The evolution was independent of tumor marker levels and the type of chemotherapy regimen. The SAPS II score did not accurately describe the severity of this population. The only predictor of intubation was the initial PaO2/FiO2 ratio upon admission to the ICU. Six out of seven patients who did not require MV were discharged alive from the hospital, whereas all but one patient requiring MV died. Refractory hypoxemia and ventilator-associated pneumonia were the leading causes of death. CONCLUSIONS: Acute respiratory distress in patients with lung metastases from NSGCT is a rare cause of ARDS. Chemotherapy could be responsible for triggering the respiratory worsening. Patients with severe respiratory insufficiency (PaO2 <70 mmHg on room air) on admission to hospital should be promptly transferred to the ICU for the first chemotherapy course.

Adult↗
PubMed2001

Metachronous gonadal and extragonadal primaries, or late relapse of germ cell tumor?

We report five distinct cases of apparently metachronous extragonadal and gonadal germ cell tumors (GCT) occurring in the same patient. Two patients had metachronous GCT of the central nervous system and the testis. One of these patients had been successfully treated for a germinoma of the pineal gland and developed a nonseminomatous GCT of the testis 10 years later. The second patient had a primary seminoma of the testis treated by orchiectomy followed by radiotherapy and developed a germinoma of the sphenoidal sinus 17 months later. Three other patients had an apparently metachronous retroperitoneal and testicular GCT with 22, 44, and 66 months elapsing, respectively, between the first and second neoplasms. These cases suggest that the remaining testis is not only at risk for a second primary GCT, but that a second GCT may emerge at an extragonadal site. A genetic predisposition may account for some of these cases and the occurrence of bilateral testicular GCT. In none of these cases, however, could we ascertain whether testicular GCT was truly a second primary or a relapse of a "primary" retroperitoneal GCT in our cases.

Journal Article↗
PubMed2000

Phase II EORTC trial with 5-fluorouracil, cisplatin and interferon-alpha as second-line treatment of advanced transitional cell cancer of the urothelial tract.

BACKGROUND: Based on the favorable results of the combination 5-fluorouracil (5-FU), cisplatin and interferon-alpha as second-line treatment in advanced metastatic transitional-cell carcinoma of the urothelial tract a confirmatory study was executed in a multicenter setting. PATIENTS AND METHODS: In this open label phase II study 43 patients failing adequate previous chemotherapy were treated with IFN-alpha2b 5 MU/m2 subcutaneously for 5 consecutive days starting on day 1 and 22 simultaneous with 5-FU 500 mg/m2 daily as a continuous infusion. In between the same dose of IFN-alpha2b was given 3 times weekly with CDDP 25 mg/m2 on days 1, 8, 15 and 22. This cycle was repeated every six weeks. RESULTS: In 40 eligible patients 5 PR were seen (12.5%; 95% confidence interval (95% CI): 4.1%-26.8%). The major toxicity was hematological. Two toxic deaths were seen due to gastrointestinal hemorrhage. CONCLUSIONS: In view of these results this combination can not be recommended as second line treatment for metastatic transitional-cell carcinoma of the urothelial tract.

Aged↗
PubMed2000

Peritoneal carcinomatosis in germ-cell tumor: relations with retroperitoneal lymph node dissection.

Peritoneal carcinomatosis from germ-cell tumor has rarely been described, and thus remains largely unknown. We report here five cases involving this entity. All five patients had embryonal carcinoma in their primary germ-cell tumor. Four of them had undergone retroperitoneal lymph node dissection (RPLND), and viable malignant cells were found. RPLND was performed for relapses (n = 3) and as primary therapy for stage II disease (n = 1). The peritoneum was the only site of relapse in three patients, and was associated with pleural effusion in one. The time to relapse after RPLND ranged from 6 to 14 months. One patient sustained injury to lymph nodes during RPLND, and another patient had a peritoneal xanthelasma. The only three patients already described in the literature underwent RPLND or surgical biopsy. All these observations suggest a striking relation between RPLND and occurrence of subsequent peritoneal carcinomatosis.

Adult↗
PubMed2000

Determination of plasma methoxyamines.

The determination of plasma methoxyamines is the most informative parameter for the diagnosis of pheochromocytoma. Very good sensitivity and specificity are necessary for this. The measurement of deconjugated (free plus sulfate-conjugated) metanephrines is more useful. Concentrations are 10-fold higher than free metanephrine concentrations. The methodology generally uses a column purification and high performance liquid chromatography with electrochemical detection. We have tested six commercial columns used for the purification step. We chose a rapid and reliable method with a mixture of strong cation-exchange and strong anion-exchange groups bonded onto a silica column. This protocol has been validated with samples of plasma from normal subjects, healthy elderly people, renal failure patients and patients with pheochromocytoma.

Chromatography, High Pressure Liquid↗
PubMed2000

[Fluorodeoxyglucose (FDO) positron emission tomography (PET) in testicular germ cell tumors in adults: preliminary French clinical evaluation, development of the technique and its clinical applications].

OBJECTIVES: Metabolic positron emission tomography (PET) is a new imaging modality for the detection of tumours, which uses fluorodeoxyglucose (FDG) to demonstrate increased carbohydrate metabolism of malignant cells. The management of testicular germ cell tumours in adults raises three clinical problems poorly resolved by conventional imaging techniques: identification of suspected recurrences in a context of elevated circulating serum markers, initial staging assessment after orchidectomy, evaluation of the response to treatment. MATERIAL AND METHODS: The authors report the data obtained in 16 patients (6 cases of seminoma and 10 cases of non seminomatous germ cell tumour [NSGCT]), investigated in the Frédéric-Joliot Department using a dedicated PET camera, 60 minutes after intravenous injection of 270 MBq of FDG. RESULTS: In 9 cases of assessment of elevated serum markers with no tumour identified by conventional examinations, PET demonstrated images likely to correspond to tumour sites in 7 patients (5 true-positives [TP] and 2 false-positives [FP] due to postoperative inflammatory changes). PET was negative in 2 out of 9 patients, in whom subsequent follow-up showed spontaneous but delayed return to normal of tumour markers. In 3 of the 4 cases of initial staging of the disease, PET excluded an extension suspected by conventional imaging and the 4th case was a FP for PET. In 3 cases of evaluation of the response to treatment, PET concluded on the absence of viable residual tumour mass, with a false-negative result in one case. CONCLUSIONS: These results are in line with those reported in the literature, which emphasize the diagnostic difficulties encountered in this disease. The significant contribution of FDG-PET should be confirmed by larger series of patients investigated by this new modality.

Adult↗
PubMed1999

Risk factors for tuberculosis in patients with AIDS in London: a case-control study.

OBJECTIVE: To identify risk factors for the acquired immune-deficiency syndrome (AIDS) associated with tuberculosis, in patients with AIDS attending 11 of the largest human immunodeficiency virus (HIV)/AIDS Units in London. DESIGN: Case-control study nested in a retrospective cohort of 2048 HIV-1 positive patients. Cases were defined as patients with a definitive diagnosis of tuberculosis, and controls as patients with AIDS and without tuberculosis during follow-up. RESULTS: Of 627 patients diagnosed with AIDS, 121 had a definitive diagnosis of tuberculosis. Significant risk factors for tuberculosis in the univariate analysis were sex, ethnicity, age, HIV exposure category and hospital attended, and in the multiple regression analysis ethnicity, age and hospital attended. African ethnicity was the strongest risk factor for tuberculosis (adjusted odds ratio [AOR] 5.9, 95% confidence interval 3.4-10.2). The risk of tuberculosis was higher in the younger age groups (test for trend P < 0.001). The hospital-associated risk of tuberculosis was more heterogeneous in the non-African group, and non-Africans attending Hospital 1 had an increased risk of tuberculosis which was statistically significant. CONCLUSIONS: The risk factors for AIDS-associated tuberculosis in London are sub-Saharan African origin, younger age group, and, among the non-Africans only, attending one hospital in east London. Different transmission patterns and mechanisms for the development of tuberculosis may operate in different settings depending on the background risk of tuberculous infection. Screening for tuberculosis infection and disease among HIV-positive individuals in London is important for the provision of preventive or curative therapy, and prophylaxis policies need to be designed in accordance with the transmission patterns and mechanisms of disease.

Acquired Immunodeficiency Syndrome↗
PubMed1999

[Place of chemotherapy in the treatment of invasive bladder tumors].

Urothelial bladder tumours are chemosensitive. Chemotherapy is indicated in the case of metastatic bladder cancer. The M-VAC protocol remains the reference treatment. The efficacy of this protocol is estimated to be about 18% in terms of complete responses and 20% of these responding patients achieve long-term survival. New combinations, comprising drugs such as ifosfamide, gallium nitrate, paclitaxel or gemcitabine, appear to be promising. Neoadjuvant and adjuvant chemotherapy cannot be considered to be standard treatment at the present time.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Disease progression and survival following specific AIDS-defining conditions: a retrospective cohort study of 2048 HIV-infected persons in London.

OBJECTIVE: To assess the impact of specific AIDS-defining conditions on survival in HIV-infected persons, with emphasis on the effect of tuberculosis. METHODS: A retrospective cohort analysis of HIV-infected Africans and non-Africans attending 11 specialist HIV/AIDS units in London enrolled for a comparison of the natural history of HIV/AIDS in different ethnic groups. RESULTS: A total of 2048 patients were studied of whom 627 (31%) developed 1306 different AIDS indicator diseases. Pneumocystis carinii pneumonia accounted for 159 (25%) of initial AIDS episodes and tuberculosis for 103 (16%). In patients with HIV disease, tuberculosis had the lowest risk [relative risk (RR), 1.11; 95% confidence interval (CI), 0.75-1.63], and high-grade lymphoma had the highest risk (RR, 20.56; 95% CI, 2.70-156.54) for death. For patients with a prior AIDS-defining illness, the development of subsequent AIDS indicator diseases such as Pneumocystis carinii pneumonia (RR, 1.18; 95% CI, 0.77-1.83) and tuberculosis (RR, 1.36; 95% CI, 0.76-2.47) had the best survival, and non-Hodgkin's lymphoma had the worst survival (RR, 9.67; 95% CI, 1.26-74.33). Patients with tuberculosis had a lower incidence of subsequent AIDS-defining conditions than persons with other initial AIDS diagnoses (rate ratio, 0.47; 95% CI, 0.37-0.59). CONCLUSIONS: Considerable variation exists in the relative risk of death following different AIDS-defining conditions. The development of any subsequent AIDS-defining condition is associated with an increased risk of death that differs between diseases, and this risk should be considered when evaluating the impact of specific conditions. Like other AIDS-defining conditions, incident tuberculosis was associated with adverse outcome compared with the absence of an AIDS-defining event, but we found no evidence of major acceleration of HIV disease attributable to tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1998

Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients.

BACKGROUND: Very few series have reported indications for and results of hepatectomy for isolated unique or multiple liver metastases (LM) from a noncolorectal primary. We performed a prospective analysis of 147 patients submitted to hepatectomy for LM to evaluate the results and indications for this unusual type of treatment. STUDY DESIGN: Of 538 patients submitted to hepatectomy for a malignant tumor between 1984 and 1996, 147 underwent operations for noncolorectal LM. Conventional and unconventional hepatectomy procedures were used with intermittent clamping of the hepatic pedicle, and in some patients with intermittent vascular occlusion of the liver. RESULTS: Postoperative hospital mortality was 2%. The crude 5-year survival was 36%, and survival without progressive disease was 28%. No difference was observed in survival when synchronous and metachronous LM were compared, or when patients with more or fewer than three LM were compared. Five-year survival rates were 20% for 35 breast cancers, 74% for 27 neuroendocrine tumors, 46% for 20 testicular tumors, 18% for 13 sarcomas, and slightly less than 20% for 11 gastric carcinomas, 10 melanomas, and 7 tumors of the gallbladder, according to the primary. Survival exceeded 20% for 6 gynecologic tumors but was disappointing for head and neck cancers, when the primary was unknown, or when the tumor was truly undifferentiated. CONCLUSIONS: Certain guidelines emerge from this series on the indications and uses of adjuvant chemotherapy. Indications for hepatectomy are relatively straightforward for neuroendocrine, testicular, and renal tumors. Hepatectomy for LM from other primaries appears beneficial in certain sarcomas, breast and gynecologic cancers, and perhaps melanoma, for which selection criteria, unfortunately, remain obscure.

Adolescent↗