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T A Splinter

Publications and source records attributed to T A Splinter.

At least 37 records · Page 2Linked to original sources
PubMed1996

Serum neuron-specific enolase (S-NSE) and the prognosis in small-cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres.

The influence of pretreatment serum neuron-specific enolase (S-NSE) in addition to more conventional prognostic factors on survival duration in small-cell lung cancer (SCLC) was investigated in 770 patients from nine centres in six countries. The other variables included stage of disease, performance status (PS), age, sex, serum lactate dehydrogenase (S-LDH), serum alkaline phosphatase (S-AP), and serum carcinoembryonic antigen (S-CEA). Increased values of S-NSE (> 12.5 micrograms-1 l) were observed in 81% of the patients, whereas S-LDH, S-AP and S-CEA were elevated in only half of the patients or less. Multivariable analysis by Cox's proportional hazard model disclosed S-NSE as the most powerful prognostic factor followed by poor PS and extensive stage disease. If PS was ignored, S-LDH came up as a significant prognostic factor. S-AP, S-CEA, age and sex had no significant influence on the prognosis. The three prognostic factors, S-NSE, PS and stage of disease, enabled establishment of a prognostic index (PI) based on a simple algorithm PI = zNSE + z(stage) + 2zPS. This segregated the patients into four groups with clearly different prognosis. The median survival and 95% confidence intervals of the four groups were: 468 days (540-408), 362 days (405-328), 256 days (270-241) and 125 days (179-58). Based on the present results we recommend S-NSE and PS, in addition to stage, for prognostic stratification in treatment trials on SCLC.

Adult↗
PubMed1996

Cisplatin and etoposide in oesophageal cancer: a phase II study. Rotterdam Oesophageal Tumour Study Group.

In the search for effective chemotherapy regimens which can be used in multimodality treatment programmes for patients with cancer of the oesophagus, we conducted a phase II trial to determine the activity and toxicity of the combination of cisplatin and etoposide in patients with advanced squamous cell carcinoma of the oesophagus. Seventy-three consecutive patients with unresectable or metastatic squamous cell carcinoma of the thoracic oesophagus were treated with cisplatin 80 mg m-2 by 4 h infusion on day 1, etoposide 100 mg (fixed dose) by 2 h infusion on day 1 and 2, and etoposide 200 mg m-2 orally on day 3 and 5. Courses were repeated every 4 weeks, for a maximum of six courses. The oral dosages of etoposide were modified individually until a significant degree of myelosuppression was reached. Of 65 evaluable patients, five complete responses (CRs) and 26 partial responses (PRs) were seen, for an overall response rate of 48% (95% confidence interval 35-60%). Median time to progression was 7 months (range 3-72 + months). There were two toxic deaths (neutropenic sepsis). The response rate equals that of other cisplatin-based regimens. Its toxicity profile allows addition of a third active drug such as 5-fluorouracil.

Adult↗
PubMed1996

5-fluorouracil and folinic acid in advanced adenocarcinoma of the esophagus or esophago-gastric junction area. Rotterdam Esophageal Tumor Study Group.

BACKGROUND: The results of chemotherapy against gastric cancer or esophageal squamous cell carcinomas cannot be generalized to adenocarcinomas of the esophagus. Therefore the combination of 5-fluorouracil and folinic acid was studied in esophageal adenocarcinoma. PATIENTS AND METHODS: After a loading dose of 4 x 90 mg folinic acid orally, a continuous infusion of 5-fluorouracil 500 mg/sqm/day for 5 days with concommitant folinic acid 6 x 60 mg/day orally, was administered to 29 consecutive patients with metastatic adenocarcinoma of the esophagus or esophagogastric junction area. RESULTS: This schedule was tolerated well with mild mucositis and diarrhea. In one patient reversible cardiotoxicity was seen. Five patients obtained a partial remission (19%; 95% confidence interval (CI): 6%-38%), and 8 patients stable disease. One early death. CONCLUSIONS: This combination has modest activity against adenocarcinoma of the esophagus; its toxicity profile permits incorporation in combination protocols.

Adenocarcinoma↗
PubMed1996

Two schedules of teniposide with or without cisplatin in advanced non-small-cell lung cancer: a randomized study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: We conducted a randomized trial to investigate the value of the addition of cisplatin to teniposide (VM26) and to investigate the schedule dependence of the topoisomerase II inhibitor VM26, in advanced non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Two hundred twenty-five NSCLC patients were randomized to receive VM26 120 mg/m2 on days 1, 3, and 5 or 360 mg/m2 on day 1 only, either as a single drug or in combination with cisplatin 80 mg/m2 on day 1. Cycles were repeated every 3 weeks. Response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. RESULTS: The response rate of the two cisplatin-containing arms was superior to that of the two arms that contained VM26 only (22% v 6%, P < .001); progression-free survival and survival times were also longer in the cisplatin-containing arms (median, 4.3 v 2.2 months, P = .003; median 7.2 v 5.9 months, P = .008, respectively). Toxicity was significantly higher in the cisplatin-containing arms; the most frequent side effects were leukopenia, nausea and vomiting, and alopecia. The schedule of VM26 did not significantly influence the response rate, progression-free survival interval, or survival duration. However, the response rate of the 1-day administration was significantly lower than that of the 3-day administration when given as single drugs. CONCLUSION: The addition of cisplatin to VM26 improves the response rate, progression-free survival interval, and survival duration over VM26 alone, although at the cost of a significant increase in toxicity. Cisplatin should be considered as the basis for combination chemotherapies in advanced NSCLC.

Adult↗
PubMed1996

Results of the phase II EORTC study comparing paclitaxel/cisplatin with teniposide/cisplatin in patients with non-small cell lung cancer. EORTC Lung Cancer Cooperative Group.

Toxicity and response rates are evaluated in a randomized phase II study comparing paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin with teniposide/cisplatin in the treatment of non-small cell lung cancer to decide whether this study should continue as a phase III trial. A response was seen in 26% (10 of 38) of the patients receiving teniposide/cisplatin and in 40% (14 of 35) of those receiving paclitaxel/cisplatin. Overall, evidence of toxicity was more severe in the cisplatin/teniposide group, especially with regard to myelotoxicity. Grade 4 neutropenia was seen in 66% of patients receiving teniposide compared with 29% of those treated with paclitaxel/cisplatin. The study is to continue as a phase III trial, with 150 patients expected to participate in each treatment group.

Adult↗
PubMed1996

Paclitaxel and carboplatin as neoadjuvant chemotherapy in operable (stage I and II) and locally advanced (stage IIIA-N2) non-small cell lung cancer.

In 1995, a randomized intergroup study of neoadjuvant chemotherapy followed by either surgery or radiotherapy in the treatment of non-small cell lung cancer was started under the auspices of the European Organization for Research and Treatment of Cancer (EORTC 08941). The objective of this study is to investigate whether surgery or radiotherapy represents superior locoregional treatment, in terms of survival and quality of life, for patients with stage IIIA(N2) non-small cell lung cancer who have achieved a response after three courses of neoadjuvant chemotherapy. A phase II side study will investigate the clinical and pathologic response rate (if applicable), as well as acute and late side effects during or after consecutive surgery and/or radiotherapy of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin. It is planned that paclitaxel 175 mg/m2 will be given as a 3-hour infusion, followed by a 30-minute infusion of carboplatin at a dose based on a target area under the concentration-time curve of 6 mg x min/mL. This phase II study was started in October 1996. Depending on the response rate and early and late side effects observed in this well-defined, prognostically favorable group of patients, it will be decided whether and how to use the same combination chemotherapy in an ongoing randomized trial currently being conducted by the Dutch Lung Cancer Study Group (DLCSG 94-2). In the latter trial, patients with stage I and II non-small cell lung cancer are randomized to immediate surgery or two courses of neoadjuvant chemotherapy. Responding patients will receive another two courses of chemotherapy before surgery; nonresponders will go directly to surgery.

Antineoplastic Agents, Phytogenic↗
PubMed1995

Disease monitoring by the tumour markers cyfra 21.1 and TPA in patients with non-small cell lung cancer.

We evaluated the use of two tumour markers Cyfra 21.1 and tissue polypeptide antigen (TPA) for disease monitoring. Assessment of response to WHO criteria was compared to response assessment according to changes in the tumour marker levels. The criteria defined for marker response were a 65% decrease for a partial response and a 40% increase for progressive disease. When response evaluations with a positive lead time were included, 72% of 115 evaluations for Cyfra 21.1 and 59% of 107 evaluations for TPA yielded the same result. Most discordant evaluations were caused by those evaluations whereby the patient achieved a partial response according to the WHO criteria and had normalisation of the marker. Less cases with a positive lead time, more negative lead times, and more patients with progressive disease without an increase of the marker were seen with TPA compared to Cyfra 21.1. In conclusion, Cyfra 21.1 follows the changes in the tumour load better than TPA. Rising levels of both markers nearly always indicate disease progression, and such knowledge easily obtained may prevent the continuation of ineffective treatment.

Adult↗
PubMed1995

Mitoxantrone in metastatic apudomas: a phase II study of the EORTC Gastro-Intestinal Cancer Cooperative Group.

We performed a phase II study with mitoxantrone in patients with carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid. Thirty-five eligible patients received mitoxantrone 12 mg m-2 i.v. every 3 weeks. Among 18 previously untreated patients, three responded (17%, 95% CI = 4-41%); no responses were achieved in 17 previously treated patients. Of the 21 patients who had carcinoid tumours, 11 were previously untreated and two achieved a response (18%, 95% CI = 2-52%). Overall response rate was 9% (95% CI = 2-23%). At a median follow-up of 43 months, median overall survival was 16 months. The median survival of 21 patients with a normal alkaline phosphatase was 29 months and 9 months for 14 patients with elevated serum levels (P = 0.005). A similar observation was noticed for gamma-glutamyltransferase (P = 0.007). We concluded that mitoxantrone is not active in APUD tumours. Elevated alkaline phosphatase and gamma-glutamyltransferase are associated with a poor prognosis.

Adenoma, Islet Cell↗
PubMed1994

The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial.

The efficacy of the ACTH (4-9) analogue Org 2766 in the prevention of subclinical cisplatin neuropathy was assessed in a double-blind placebo-controlled multi-centre study in patients with testicular cancer or adenocarcinoma of unknown primary. Forty-two patients received at least four cycles of cisplatin (100 mg/m2 per cycle), together with subcutaneous injections of Org 2766 (2 mg/day for 5 consecutive days) or placebo. Vibratory threshold was used as a measure of neuropathy. For each individual patient, the influence of cisplatin on vibratory perception was quantified by the slope of the regression line between the natural logarithm of the vibratory thresholds and the number of cycles. From the slopes, the proportional increase of vibratory threshold per cycle of cisplatin was calculated. On average, vibratory thresholds increased by 42% with each cycle of 100 mg/m2 of cisplatin in the placebo group, and by 19% during treatment with Org 2766. The influence of cisplatin on vibratory thresholds was highly significant in the placebo group (P < 0.0001), and of borderline significance in the group treated with Org 2766 (P = 0.06). The difference in slopes between the two groups was of borderline statistical significance (Wilcoxon's two-sample test: P = 0.06; analysis of variance: P = 0.04). These results show that Org 2766 cannot completely prevent cisplatin neuropathy in young men with testicular cancer, but nerve damage may be ameliorated by the use of this ACTH (4-9) analogue.

Adenocarcinoma↗
PubMed1994

Prognostic significance of tissue polypeptide-specific antigen (TPS) in patients with advanced non-small cell lung cancer.

In this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate dehydrogenase (LDH), gamma-glutamyltranspeptidase and alkaline phosphatase, and the median level of TPS in patients with stage 4 disease was significantly higher as compared to stage 3A and 3B disease. In the univariate analysis, performance status, stage of disease, LDH, alkaline phosphatase, a histology of undifferentiated large cell carcinoma and TPS all had a statistically significant association with survival. Multivariate analysis showed that stage of disease, performance status, histology and TPS were the most important prognostic factors. TPS has prognostic significance for survival in patients with advanced NSCLC, independent from performance status and stage of disease.

Adult↗
PubMed1994

Evaluation of a new tumour marker in patients with non-small-cell lung cancer: Cyfra 21.1.

The Cyfra 21.1 assay is a newly developed test which measures in serum a fragment of cytokeratin 19. We evaluated this marker in 212 patients with non-small-cell lung cancer (NSCLC), predominantly stage 3a-b and 4, and compared it with three other markers: carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA). Sensitivities for Cyfra 21.1, TPA, CEA and SCC (using cut-off levels corresponding to a 95% specificity for benign lung diseases) were 40%, 40%, 42% and 19% respectively. The sensitivity of CEA was significantly higher in patients with adenocarcinomas compared with the other three markers, while the sensitivity of Cyfra 21.1 and TPA was significantly higher in patients with squamous cell carcinomas. The value of Cyfra 21.1 for monitoring disease during chemotherapy could be evaluated in 23 patients with squamous cell carcinomas. When the cases of lead time were included a concordance between clinical evaluations according to WHO response criteria and evaluations according to changes in the marker levels of 74% was found. The criteria defined for marker response were a 65% decrease in the marker level for a partial response and a 40% increase for progressive disease. In particular, increasing levels of this marker indicated usually disease progression. In conclusion, Cyfra 21.1 is a useful serum marker for patients with NSCLC, especially for disease monitoring of patients with squamous cell carcinoma during and after chemotherapy.

Adult↗
PubMed1994

Phase II study of carboplatin and etoposide as a first line regimen in patients with metastatic breast cancer.

BACKGROUND: The data available on the role of carboplatin and etoposide in breast cancer, especially in patients with no or minimal prior therapy are limited. PATIENTS AND METHODS: We performed a phase II study with carboplatin and etoposide as first line treatment in 34 patients with metastatic breast cancer. The treatment regimens was carboplatin 300 mg/m2 day 1, and etoposide 100 mg/m2 days 1, 3 and 5 every four weeks. RESULTS: Of 33 evaluable patients, 2 achieved complete responses (6%) lasting 4 and 5 months, 7 patients (21%) achieved partial responses with a median duration of 6+ (range 5-8) months, 15 patients had stable disease, and 9 progressed during treatment. The major toxicity was myelosuppression WHO grades 3 or 4 leukocytopenia or thrombocytopenia were seen in 15 and 10 patients, respectively. One formally ineligible patient with an impaired renal function died 14 days after the start of treatment because of a septicaemia in the presence of a grade 4 leukocytopenia. Besides this patient no other patient presented with granulocytopenic fever. CONCLUSION: In view of the observed response rate of 27% (95% confidence interval 11%-43%) we think that carboplatin and etoposide given in this dose and schedule has probably no clear advantage over the more commonly used regimens.

Adult↗
PubMed1994

Acute antiemetic efficacy and safety of dolasetron mesylate, a 5-HT3 antagonist, in cancer patients treated with cisplatin. European Dolasetron Study Group.

Dolasetron mesylate (MDL 73,147EF), a new serotonin receptor (5-HT3) antagonist was administered to 164 cancer patients naive or non-naive to chemotherapy, in single, rising doses of 10, 20, 30, 40, or 50 mg i.v. 15 minutes prior to an infusion of cisplatin. The severity of nausea and number of episodes of emesis were recorded during the 24-hour period following cisplatin administration. There were significant differences between the dose groups, sex, and naive and non-naive patients. There were also significant dolasetron dose-dependent differences for no emesis (p = .01), less than 3 emetic episodes (p = .01), time-to-onset of nausea (p = .04), and time-to-onset of emesis (p = .003). The severity of symptoms was greater for females, for patients with previous chemotherapy, and with shorter duration of cisplatin infusion. Adjustment for these variables and the study center reduced the associations between the dose of dolasetron mesylate and the outcome variables. The principal adverse events were headache (11%) and diarrhea (6%). Dolasetron mesylate was well tolerated; a single dose of 40 or 50 mg controlled acute nausea and vomiting induced by highly emetogenic chemotherapy in the majority, in particular in chemotherapy-naive and male patients. In conclusion, 50 mg and a larger dose merit study in controlled trials with stratification for sex and previous chemotherapy.

Adult↗