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Biomedical subjects

G Vandermoten

Publications and source records attributed to G Vandermoten.

At least 19 recordsLinked to original sources

[Small cell bronchial cancer. Comparison of results of weekly polychemotherapy using multiple drugs with standard chemotherapy. European Lung Cancer Working Party].

The administration of multiple cytostatic drugs on a weekly basis has been proposed as a new intensive chemotherapy modality for small-cell lung cancer. The European Lung Cancer Working Party has conducted a randomized trial comparing to a standard regimen (cyclophosphamide + adriamycin + etoposide given at the cycle beginning) a weekly chemotherapy with 7 active drugs (cyclophosphamide + adriamycin + etoposide on day 1; cisplatin + vindesine on day 8; methotrexate + vincristine on day 15). A total of 215 eligible patients have been registered. There has been no significant difference between the 2 arms for response and for survival. The total relative dose-intensity has been lower in the weekly chemotherapy arm. This approach has failed to improve current results.

Adult↗

Multiple-drug weekly chemotherapy versus standard combination regimen in small-cell lung cancer: a phase III randomized study conducted by the European Lung Cancer Working Party.

PURPOSE: A randomized trial was conducted in patients with small-cell lung cancer (SCLC) to determine if survival can be improved by a weekly chemotherapy regimen combining various drugs. PATIENTS AND METHODS: Two hundred twenty-three patients were randomized to receive either six courses of a multiple-drug combination (MDC) regimen (Adriamycin [ADR; doxorubicin; Farmitalia Carlo Erba, Milan, Italy] 25 mg/m2 intravenously [i.v.] on day 1; etoposide [VP16] 120 mg/m2 i.v. on day 1; cyclophosphamide [CPA] 500 mg/m2 i.v. on day 1; cisplatin 60 mg/m2 i.v. on day 8; vindesine [VDS] 3 mg/m2 i.v. on day 8; vincristine [VCR] 2 mg i.v. on day 15; methotrexate [MTX] 100 mg/m2 i.v. on day 15), or a standard chemotherapy (SC) regimen (ADR 50 mg/m2 i.v. on day 1; CPA 1 g/m2 i.v. on day 1; VP16 80 mg/m2 i.v. on days 1 to 3). RESULTS: In 98 MDC-treated and 101 SC-treated assessable patients, we observed 69% and 62% objective responses rates, respectively. There was no significant difference in survival, with median durations and 2-year overall survival rates of 49 and 43 weeks and 8.5% and 7.9%, respectively. There was a significant increase in response rate in favor of MDC patients with limited disease (84% v 62%). Toxicity was tolerable, although SC was more hematotoxic, with 76% (v 59%) experiencing leukopenia and 17% (v 7%) experiencing thrombocytopenia (grades III and IV). If the cumulative doses received were nearly equal to the scheduled cumulative doses in both arms, the total relative dose-intensity (RDI) was significantly higher in the SC arm. The difference was due to increased treatment delays in the MDC arm. CONCLUSION: Weekly MDC failed to improve survival rates in patients with SCLC.

Adult↗

A randomized study comparing etoposide and vindesine with or without cisplatin as induction therapy for small cell lung cancer. EORTC Lung Cancer Working Party.

We conducted a randomized trial testing etoposide (120 mg/m2 d1-3) + vindesine (3 mg/m2 d1) with or without cisplatin (60 mg/m2 d1) in patients with SCLC. A total of 8 courses were given at 3-week intervals. 221 patients were registered and 201, 95 in the CEV arm and 106 in the EV arm, were eligible for survival analysis. 183 patients were evaluable for response: 74% had an objective response (OR) with CEV versus 55% with EV (p = 0.01). Complete response rates were, respectively, 21% and 13% (NS). In patients with limited disease (LD), OR rates were 72% and 61% (NS), and 76% and 48% in extensive disease (ED) (p = 0.01). There was no statistically significant difference in survival between the two regimens (p = 0.745, log rank test). Median survival for EV and CEV were, respectively, 40 and 45 weeks, and two-year survivals were 11% and 9%; in patients with LD, the corresponding figures were 14% and 16% (NS) and in those with ED, 8% and 3% (NS). Disease extent (LD vs ED), Karnofsky performance status and loss of body weight were significant prognostic factors for survival; age, sex, type of treatment and type of lesion were not. The CEV regimen was not significantly more myelotoxic than EV but was associated with more severe nausea, vomiting and alopecia. In conclusion, the addition of cisplatin to the EV regimen, a combination reported to be easily manageable, was associated with a significantly higher OR rate but survival was not significantly improved.

Adult↗

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861.

The European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Working Party conducted a randomized trial comparing cisplatin (CDDP; 120 mg/m2, day 1) and carboplatin (CBDCA; 325 mg/m2, day 1) in combination with etoposide (VP16; 100 mg/m2, days 1, 2, and 3) in advanced non-small-cell lung cancer (NSCLC). Two hundred twenty-eight patients were eligible for survival and 202 assessable for response. We obtained 27 of 100 objective responses (ORs; 27%) in the CDDP arm and 16 of 102 (16%) in the CBDCA arm (P = .07). There was no significant difference in survival. Toxicity, consisting mainly of myelosuppression and renal function impairment, was significantly increased in the patients receiving the CDDP treatment. We conclude that CDDP plus VP16 was more active but also more toxic than CBDCA plus VP16 in advanced NSCLC.

Adult↗

A randomized trial of two platinum combinations in patients with advanced non-small cell lung cancer: a preliminary report. European Organization for the Research and Treatment of Cancer--Lung Cancer Working Party.

A randomized study with cisplatin (120 mg/m2) or carboplatin (325 mg/m2) plus etoposide (100 mg/m2, days 1 to 3) in 162 evaluable patients with advanced non-small cell lung cancer (NSCLC) compared response and survival after treatment. No statistically significant difference in survival rates was detected; median survival was 25 weeks for patients receiving cisplatin and 24 weeks for those receiving carboplatin. The objective response rate was 25% for cisplatin plus etoposide and 20% for carboplatin plus etoposide. Granulocytopenia, diarrhea, and nephrotoxicity were significantly more frequent with cisplatin plus etoposide than with carboplatin plus etoposide. Severe nausea and/or vomiting occurred during 59 of 77 courses (77%) with cisplatin and 48 of 75 (64%) with carboplatin (P = .13). Unlike cisplatin plus etoposide, carboplatin plus etoposide was administered on an outpatient basis. At the dose used in the present study, carboplatin plus etoposide was as effective as but less toxic than cisplatin plus etoposide for NSCLC and could be given more easily.

Adenocarcinoma↗

Cisplatin versus cisplatin plus etoposide in the treatment of advanced non-small-cell lung cancer. Lung Cancer Working Party, Belgium.

We conducted a randomized study comparing the survival after treatment with cisplatin (120 mg/m2) or cisplatin plus etoposide (100 mg/m2 on days 1, 2, and 3) in 162 evaluable patients with advanced non-small-cell lung cancer (NSCLC). No statistically significant difference in survival was detected; the median survival was 26 and 22 weeks, respectively, for patients receiving cisplatin and for those receiving cisplatin plus etoposide. The objective response rate was 19% for cisplatin and 26% for the combination; the corresponding response rates were 17% and 43% in patients with limited disease. No significant differences were detected between the two study arms as far as toxicity was concerned, except for alopecia and granulocytopenia, which occurred more frequently in patients treated with cisplatin plus etoposide.

Adenocarcinoma↗

Oral etoposide preceding cisplatin in advanced non small cell lung cancer (NSCLC). A phase II study.

Forty male patients with locally advanced (LD; 11 patients) and extensive (ED; 29 patients) NSCLC were treated with oral etoposide (240 mg/m2 days 1-3) preceding intravenous cisplatin (100 mg/m2 day 4) at 4 weekly intervals. Eleven patients achieved major response (27.5%; 1 CR, 10 PR). Minor response (MR) occurred in seven patients (17.5%); stable disease (SD) in seven patients (17.5%) and progressive disease (PD) in 15 (37.5%). The median duration of response in major responders was 31 weeks. The median survival time (MST) in all patients was 42 weeks. Patients achieving response, and stable disease lived significantly longer than progressors (P less than 0.0001; 56 vs. 9 weeks respectively). The MST of non-progressors in both LD and ED was significantly increased as compared to progressors. Two patients with poor risk prognostic variables died from myelosuppression-related infection early during the first course of chemotherapy. The remainder of the courses were without severe hematological complications. Alopecia was the most common side-effect. Gastro-intestinal, neurological and renal complications were mild to moderate. Intravenous etoposide can be replaced by the oral formulation with preservation of antitumoral activity in NSCLC patients, offering the advantage of maximal treatment outside the hospital.

Adult↗

Phase II study of an intensive combination chemotherapy with cisplatin, adriamycin, etoposide and cyclophosphamide (CAVE) in small cell lung cancer.

One hundred and twelve patients with small cell lung cancer (SCLC) were treated with a combination (CAVE) of cisplatin (60 mg/m2 day 1), adriamycin (45 mg/m2 day 1), etoposide (80 mg/m2 days 1-2-3) and cyclophosphamide (1 g/m2 day 1) given every 4 weeks. A total of 10 courses were given. Response evaluation was initially evaluated after the first two courses of CAVE and repeated at least after treatment completion. This regimen was associated with severe hematological toxicity, mainly leucopenia; five toxic deaths related to sepsis were observed. One hundred and one patients were evaluable for response: 63 with limited disease and 49 with extensive disease. Overall complete and partial response rates after the first two courses of chemotherapy were 16% and 63% respectively but 14 late complete responses were documented, leading to a 30% total complete response rate; 38% in patients with limited disease and 19% in those with disseminated disease. Median overall survival was 46 weeks with a 17% 2 year survival. The only significant prognostic factor for survival was the type of response. There was no survival difference between 'early' and 'late' complete responders. Complete responders had a 75 week median survival time with a 34% 2 year survival. CAVE is thus an effective regimen for SCLC, but with a considerable toxicity.

Adult↗

Increased plasma motilin concentrations in small cell carcinoma of the lung.

Plasma samples from 21 patients with small cell carcinoma of the lung were screened for pancreatic polypeptide, somatostatin, motilin, and vasoactive intestinal polypeptide. One patient had severe impairment of both renal and liver function. In the 20 remaining subjects vasoactive intestinal polypeptide concentrations were normal, and only two patients had increased concentrations of somatostatin. Increases in pancreatic polypeptide were detected more commonly (7/20), but these may have been non-specific age related increases. The major finding was high concentrations of motilin (greater than 496 pg/ml) in 17 of 20 patients. Plasma motilin was subsequently assayed in 16 more patients with lung cancer, including 10 patients with non-small cell carcinoma of the lung. At concentrations over 900 pg/ml plasma motilin appears to be a tumour marker for small cell carcinoma of the lung with acceptable sensitivity (59%) and specificity (78%). The origin of increased plasma motilin in small cell carcinoma of the lung was investigated. Bombesin (gastrin releasing peptide), a peptide known to stimulate the release of motilin in man, was, as in previous studies, detected in tumour but not in plasma, except in one patient out of 21. Immunohistochemical studies failed to detect motilin antigen in biopsy samples. Motilin tumour content was found to be low in tumour tissue from three patients with small cell carcinoma of the lung who had appreciable hypermotilinaemia and from three patients with non-small cell carcinoma of the lung who had either normal or slightly raised plasma motilin concentrations. The stimulus to motilin secretion in patients with small cell carcinoma of the lung remains unclear.

Adult↗

[Polychemotherapy of undifferentiated small cell bronchial cancer. Long-term results].

Long-term results of 2 studies combining etoposide and adriamycin with cisplatin (CAV) or cyclophosphamide (AVE) in small cell lung cancer indicate a 2-year survival rate of 22% and 18% respectively. The complete response rate 2 years after the onset of chemotherapy was 8% (8/98) : 11% (4/36) with CAV and 5% (4/62) with AVE. Among these 8 patients, 2 had a late relapse and one died of an unrelated cause. The actual long-term survival rate was 6% with CAV and 5% with AVE.

Adult↗

A randomized study comparing a high and a standard dose of cisplatin in combination with etoposide in the treatment of advanced non-small-cell lung carcinoma.

We conducted a randomized trial comparing a high (120 mg/m2 day 1) v a standard (60 mg/m2 day 1) dose of cisplatin in combination with etoposide (120 mg/m2 days 3, 5, and 7) in advanced non-small-cell lung carcinoma (NSCLC). Two hundred forty-one patients were evaluable for survival and 207 for response. We obtained a 25% objective response rate in the standard-dose arm and 29% in the high-dose arm; this difference was not statistically significant. There was no significant improvement in the overall survival or survival of responders with the high-dose regimen. However, toxicity (mainly myelosuppression) was significantly increased in the patients receiving the higher dose of cisplatin. An analysis of prognostic factors showed that disease progression, loss of body weight, performance status, and prior therapy were predictive parameters of survival.

Actuarial Analysis↗

Combination chemotherapy with mitomycin and vindesine in advanced non-small cell lung cancer: a pilot study by the Lung Cancer Working Party (Belgium).

The combination of mitomycin plus vindesine in advanced non-small cell lung cancer induced an objective response rate of 23% in 43 evaluable patients: 33% in nonpretreated patients (nine responses among 27 patients) and 6% in pretreated patients (one response among 16 patients). Toxicity was tolerable. We conclude that the regimen was a moderately active and easy to administer treatment for advanced non-small cell lung cancer.

Adult↗

Combination chemotherapy with adriamycin, etoposide, and cyclophosphamide for small cell carcinoma of the lung. A study by the EORTC Lung Cancer Working Party (Belgium).

The current study reports the results of Adriamycin (doxorubicin), etoposide, and cyclophosphamide (AVE) in small cell bronchogenic carcinoma. The overall rate of response was 82% in patients with limited disease and 66% in patients with extensive disease; complete remissions have been achieved in 20% of the patients with limited disease and in 7% of those with extensive disease. The median duration of survival was 14 months in patients with limited disease and 8.3 months in those with extensive disease. The results, and the analysis of literature, suggest that survival rather than response should be used to compare studies of chemotherapy in small cell bronchogenic carcinoma.

Adult↗