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M Reck

Publications and source records attributed to M Reck.

16 recordsLinked to original sources
PubMed2006

Efficacy of a toxicity-adjusted topotecan therapy in recurrent small cell lung cancer.

The present prospective multicentre trial investigated whether topotecan, given at a starting dose of 1.25 mg.m(-2) with individual dose adjustment, can improve safety in patients with relapsed/refractory small cell lung cancer without loss of efficacy. Patients received topotecan intravenously on days 1-5, every 21 days, for up to six courses. In the absence of relevant haematotoxicities, topotecan was increased to 1.5 mg.m(-2) and reduced to 1.0 mg.m(-2) in case of severe haematotoxicities. Of 170 recruited patients, 73.2% had stage IV disease and 63.4% had platinum-containing pre-treatment. Patients received a total of 521 courses. In 72.6% of those courses, the dose remained at 1.25 mg.m(-2); in 9.1% it was reduced and in 18.3% it increased. Overall response rate was 14.1% including one complete response; 28.8% had stable disease. Median duration of response was 13.6 weeks and median survival was 23.4 weeks. Clinical benefit was obvious for sensitive as well as for refractory patients. Haematotoxicity of grade 3 or 4 was clearly lower compared with the standard dose of 1.5 mg.m(-2). In conclusion, topotecan at a dose of 1.25 mg.m(-2) appears to be as effective as the dose of 1.5 mg.m(-2), but with reduced toxicity. Since patients with recurrent small cell lung cancer have a poor prognosis, they benefit especially from good tolerability.

Aged↗
PubMed2005

Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma.

BACKGROUND: A phase III trial in patients with malignant pleural mesothelioma demonstrated a survival advantage for pemetrexed plus cisplatin compared with single-agent cisplatin. Because post-study chemotherapy (PSC) may have influenced the outcome of the trial, we examined its use and association with survival. PATIENTS AND METHODS: Eighty-four patients from the pemetrexed plus cisplatin arm and 105 patients from the single-agent cisplatin arm received PSC. Kaplan-Meier survival estimates were compared by treatment groups, and by PSC and non-PSC subgroups. RESULTS: The percentage of patients receiving PSC was imbalanced between the treatment arms. Fewer pemetrexed plus cisplatin treated patients received PSC (37.2% versus 47.3%). A multiple regression analysis performed in this trial showed that PSC had a statistically significant correlation with prolonged survival (P <0.01), adjusting for baseline prognostic factors and treatment intervention. The adjusted hazard ratio for PSC over non-PSC subgroups was 0.56 (confidence interval 0.44-0.72). CONCLUSIONS: PSC in malignant pleural mesothelioma was significantly associated with prolonged survival. It is not known whether the reduced risk of death was associated with PSC or whether patients who had prolonged survival tended to receive more PSC. The pemetrexed plus cisplatin treatment group had a statistically significant survival advantage even though fewer patients from that arm of the trial received PSC. The potentially beneficial role of PSC should be assessed in prospective trials.

Adult↗
PubMed2004

Oral vinorelbine given as monotherapy to advanced, elderly NSCLC patients: a multicentre phase II trial.

Vinorelbine intravenously (i.v.) demonstrated its efficacy and tolerability in advanced non-small cell lung cancer (NSCLC) patients, including elderly subjects. Since vinorelbine is now available as an oral formulation this phase II open study was designed to evaluate its activity and tolerability in advanced, elderly NSCLC patients. A total of 56 chemonaive patients were recruited from April 2001 through to March 2002. The dosage schedule, already tested in younger NSCLC patients, was 60 mg/m(2)once a week for three weeks (first cycle), followed by 80 mg/m(2) once a week until disease progression or development of unacceptable toxicity. A limited sampling scheme was used for performing pharmacokinetic analysis on 52 of 56 patients enrolled in the study. Treatment was well tolerated with grade 3/4 neutropenia in 11/17 patients (20/30%) and febrile neutropenia in 1 (2%). Six partial responses (11%) and 25 stable disease responses were recorded, with a disease control rate of 55%. Median overall survival was 8.2 months (95% Confidence Interval (CI) [6.2-11.3]). The clinical benefit response rate was 31% on 32 evaluable patients. Pharmacokinetic profiles appeared quite similar to the historical profiles recorded following i.v. administration. Oral vinorelbine appears to be a reasonable alternative to i.v. vinorelbine, both in terms of activity and tolerability, in advanced, elderly NSCLC patients.

Administration, Oral↗
PubMed2004

[Phase II-trial of tirapazamine in combination with cisplatin and gemcitabine in patients with advanced non-small-cell-lung-cancer (NSCLC)].

Despite improvements in chemotherapy of advanced and metastatic Non-Small-Cell-Lung-Cancer (NSCLC) the prognosis of these patients still remains poor with a 5-year-survival of 2 to 5 %. Due to the high level of hypoxic cells in solid tumors agents with activity in hypoxic milieu as the Benzotriazine compound Tirapazamine (SR 259 075) might improve the therapeutic results. We treated 45 patients with advanced or metastatic Non-Small-Cell-Lung-Cancer (stage IIIb: 20 patients, stage IV: 25 patients) with the combination TPZ 330 mg/m (2) (day 1), Cisplatin 75 mg/m (2) (day 1) and Gemcitabine 1250 mg/m (2) (day 1 and 8) every 3 weeks. With a response rate of 40 % median progression free survival was 6.7 months (4.8 - 8.1 months) and median survival was 8.1 months (7.5 - 12.5 months), (1-year-survival: 35 %). Hematologic and non-hematologic toxicity was moderate (neutropenia CTC grade 3 and 4: 20 %, thrombocytopenia CTC grade 3 and 4: 16 %, nausea and vomiting CTC 3: 5 %). Treatment of advanced and metastatic NSCLC with TPZ in combination with Gemcitabine/Cisplatin was well feasible and showed results recording to currently published data. The results of a following phase III-trial are awaited.

Adult↗
PubMed2004

SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results.

BACKGROUND: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. RESULTS: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). CONCLUSION: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times.

Adult↗
PubMed2000

The Pstl polymorphism of the endotoxin-inducible heat-shock protein 70-2 gene does not affect messenger RNA level in human whole-blood cultures.

OBJECTIVE: To determine whether the human leukocyte antigen linked biallelic heat-shock protein 70-2 (HSP70-2) gene polymorphism is associated with variable HSP70-2 messenger RNA expression. DESIGN: Prospective observational study in consecutive healthy blood donors. SETTING: Department of Anesthesiology, laboratory for molecular biology in a university hospital. PARTICIPANTS: 24 healthy blood donors. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We studied the functional implication of the HSP70-2 (G/A) PstI gene polymorphism in 24 healthy, white blood donors with various HSP70-2 (G/A) genotypes by analyzing the endotoxin-inducible HSP70-2 mRNA expression by means of the reverse transcription-polymerase chain reaction. HSP70 expression was expressed semiquantitatively by calculating the ratio of HSP70-2 mRNA and the constitutively expressed glutaraldehyde 3-phosphate dehydrogenase mRNA. No significant differences in HSP70-2 mRNA expression after lipopolysaccharide (from Salmonella minnesota Re 595) stimulation were detected in individuals homozygous for the allele A (0.68, range 0.38-1, n = 10), in individuals homozygous for the allele G (0.79, range 0.42-1.1, n = 8), and in heterozygotes (HSP70-2 G/A; 0.52, range 0.4-0.67, n = 6; p > 0.05). CONCLUSIONS: The PstI polymorphism of the endotoxin-inducible HSP70-2 gene is not associated with variable HSP70-2 mRNA expression ex vivo. This finding is in accordance with the observation that HSP70-2 genotypes do not affect clinical outcome in human systemic inflammation.

Adult↗
PubMed1999

Analysis of two human leukocyte antigen-linked polymorphic heat shock protein 70 genes in patients with severe sepsis.

OBJECTIVE: To determine whether the genotype and allelic frequencies of two human leukocyte antigen-linked bi-allelic 70-kilodalton heat shock protein (HSP70) gene polymorphisms are associated with susceptibility to and outcome of severe sepsis. Furthermore, we investigated a possible linkage between HSP70 gene polymorphisms and the previously reported and mortality-related tumor necrosis factor-beta (TNF-beta) NcoI gene polymorphism. DESIGN: Consecutive entry study of patients with severe sepsis. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Eighty-seven patients with a diagnosis of severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied two bi-allelic polymorphisms within the coding region of the constitutively expressed HSP70-HOM C/T, and the stress-inducible HSP70-2 G/A in patients with severe sepsis. The HSP70-HOM Ncol, HSP70-2 Pstl, and TNF-beta NcoI polymorphisms were identified by means of the polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. No significant differences in genotype and allelic frequencies were observed for both HSP70 gene polymorphisms between the 87 patients and the 110 healthy Caucasians serving as the control group. In addition, no differences in genotype and allelic frequencies between surviving and nonsurviving patients were detected. The allelic frequencies in the group of nonsurvivors were 0.8 for the HSP70-HOM C allele and 0.2 for the HSP70-HOM T allele vs. 0.87 and 0.13 for the survivors (p > .05). The frequency for the HSP70-2 G allele was 0.36 and 0.64 for the HSP70-2 A allele in the group of nonsurvivors vs. 0.41 and 0.59 for the survivors (p > .05). Analysis of a possible linkage between HSP70 and TNF-beta genotypes resulted in a significant association (odds ratio, 4.15; p < .01) of the HSP70-2 A/A homozygous genotype and the TNFB2/B2 homozygous genotype, which is reported to be a genomic marker for a poor prognosis in severe sepsis. CONCLUSIONS: Our data show that the bi-allelic NcoI and PstI polymorphisms within the HSP70-HOM and HSP70-2 locus, respectively, are associated with neither susceptibility to nor outcome of severe sepsis. Moreover, we found a linkage between HSP70-2 A homozygotes and the previously reported and mortality-related homozygous genotype, TNFB2/B2, in patients suffering from severe sepsis.

Case-Control Studies↗
PubMed1998

[Chemotherapy of advanced non-small-cell and small-cell bronchial carcinoma with bendamustine--a phase II study].

In the palliative treatment of advanced SCLC and NSCLC there is a big need for effective and well tolerable drugs. Bendamustin is an alcylatic agent which had shown activity in the treatment of Non Hodgkin- and Hodgkin-Lymphoma as well as in the treatment of solid tumors like Mamma-Carcinoma and Colorectal-Carcinoma. We treated 21 patients with NSCLC (5 pat. Stad. III b, 16 pat. Stad. IV) and 22 pat. with Extensive Disease SCLC with Bendamustin 70 mg/m2 i.v., day 1-4 (q.28 days). We observed a response rate of 40.9% in the patients with SCLC (9 PR/40.9%), (0 CR) and no response in the patients with NSCLC. Hematologic toxicity in both groups was mild (Leucopenia WHO 1 + 2: 13 pat./30.2%, WHO 3: 2 pat./4.6%; Anemia WHO 1 + 2: 13 pat./30.2%, WHO 3: 1 pat./2.4%; Thrombopenia WHO 1 + 2: 4 pat./9.6%, WHO 3: 1/2.4%). Non Hematologic toxicity consisting of Nausea/Vomiting (WHO 2 + 3:13 pat./30.2%), Diarrhea (WHO 2 + 3:3 pat./7%), Obstipation (WHO 1 + 2: 2 pat./4.6%), Fever (WHO 1 + 2: 9 pat./20.9%) and Alopecia (WHO 1 + 2: 13 pat./31.7%, WHO 3: 1 pat./2.4%) was well tolerable. Cardiac Arrhythmias occurred in 7 pat./16.3% and PNP in 2 pat./4.6%. Treatment had to be stopped in one patient because of an allergic skin reaction. Bendamustin is a well tolerable cytostatic drug with a remarkable activity in advanced SCLC which is comparable to other well known agents in the treatment of this disease. Because of the good toxicity profile a combination with other compounds might be feasible. In advanced NSCLC Bendamustin showed no activity.

Aged↗
PubMed1992

Carboplatin/etoposide/vincristine therapy in small cell lung cancer.

Carboplatin is one of the most active agents in untreated small cell lung cancer (SCLC; 14% complete response, CR; and 61% CR + partial response, PR). The combination carboplatin/etoposide/vincristine (CEV) (phase II trial) led to an overall remission rate of 84% in patients with limited disease, with 52% CR. The median survival time with this combination was 13 months in patients with limited disease and 9.5 months in those with extensive disease. The 4-year survival rates are 26% in limited disease and 8% in extensive disease, with a plateau of the survival curve. This regimen is highly effective and exhibits low toxicity in SCLC. To evaluate the role of carboplatin in combination chemotherapy in patients with extensive SCLC, a phase III trial was performed. In this ongoing trial comparing CEV and etoposide/vincristine in SCLC patients with extensive disease, CR and overall response rates are higher in the CEV arm (CR 32 vs. 17%, CR + PR 80 vs. 60%), with statistically significant difference. In summary, chemotherapy regimens containing platinum compounds are among the most active in the treatment of SCLC. The use of the new compound carboplatin instead of cisplatin has led to similar or increased remission rates and is preferable because it has fewer side effects. Preliminary results from this ongoing, prospective, randomized phase III trial will be presented.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Combination chemotherapy with carboplatin, etoposide, and vincristine as first-line treatment in small-cell lung cancer.

PURPOSE: The antineoplastic activity of carboplatin and etoposide may be improved by the addition of vincristine (CEV) because of its low myelosuppressive potential and its activity in small-cell lung cancer (SCLC). A phase II study with CEV was carried out. PATIENTS AND METHODS: One hundred twenty-one untreated patients with SCLC (63 with limited disease [LD], 58 with extensive disease [ED]) were treated with a combination of 300 mg/m2 intravenous (IV) on day 1, etoposide 140 mg/m2 IV daily on days 1 to 3, and vincristine 1.4 mg/m2 IV on days 1, 8, and 15 every 4 weeks. RESULTS: A 90% rate overall response rate including 56% complete responses (CRs) was achieved in LD and an 83% overall response rate including 35% CRs was observed in ED. Median survival time was 13 months in limited disease and 9.5 months in extensive disease. The 24 and 36 months survival rates were 29% in LD and 9% in ED. Myelosuppression was the main form of toxicity. CONCLUSION: The combination of CEV is a new active and well-tolerated regimen in the treatment of SCLC. Prospective randomized studies of CEV with conventional chemotherapy are warranted.

Adult↗
PubMed1992

Phase II and III studies with carboplatin in small cell lung cancer.

Carboplatin is one of the most active agents in untreated small cell lung cancer (SCLC) (11% complete response [CR], 59% CR plus partial response [PR]). Combination carboplatin/etoposide/vincristine (CEV) (phase II trial) led to an overall remission rate of 84% in patients with limited disease (LD), with 52% CRs. The median survival time with this combination was 14 months in patients with LD and 9.5 months in those with extensive disease (ED). The 30-month survival rates are 30% in LD and 10% in ED, which represents a plateau of the survival curve. This regimen is highly effective and exhibits low toxicity in SCLC. To evaluate the role of carboplatin in combination chemotherapy in patients with extensive SCLC, a phase III trial was performed. In this ongoing trial comparing CEV and etoposide/vincristine in ED patients, CR and overall response rates to date are higher in the CEV arm (CR, 20% versus 15%; CR plus PR, 83% versus 65%), but as yet the differences are not statistically significant. In summary, chemotherapy regimens containing platinum compounds are among the most active in the treatment of SCLC. The use of the new compound carboplatin instead of cisplatin has led to similar or increased remission rates and is preferable because it has fewer side effects. Preliminary results from this ongoing, prospective, randomized phase III trial are presented.

Adult↗
PubMed1991

Carboplatin in small cell lung cancer.

Carboplatin is one of the most active agents in untreated small cell lung cancer (SCLC) (14% complete response [CR] and 61% CR + partial response [PR]). The combination carboplatin/etoposide/vincristine (CEV) (phase II trial) led to an overall remission rate of 84% in patients with limited disease, with 52% CR. The median survival time with this combination was 13 months in patients with limited disease and 9.5 months in those with extensive disease. The 30-month survival rates are 30% in limited disease and 10% in extensive disease with a plateau of the survival curve. This regimen is highly effective and exhibits low toxicity in SCLC. To evaluate the role of carboplatin in combination chemotherapy in patients with extensive SCLC, a phase III trial was performed. In this ongoing trial comparing CEV and etoposide/vincristine in SCLC patients with extensive disease, CR and overall response rates to date are higher in the CEV arm (CR 30% v 10%, CR + PR 90% v 75%), but as yet the differences are not statistically significant. In summary, chemotherapy regimens containing platinum compounds are among the most active in the treatment of SCLC. The use of the new compound carboplatin instead of cisplatin has led to similar or increased remission rates and is preferable because it has fewer side effects. Preliminary results from this ongoing, prospective, randomized phase III trial will be presented.

Adult↗
PubMed1990

[Chemotherapy of small cell bronchial cancer with a combination of carboplatin, vincristine and etoposide].

In a phase II study, the combination of the new platinum derivative carboplatin with vincristine and etoposide is associated with a remission rate of 81.8 per cent (LD 84.4%, ED 79.1%). The median survival rates for patients with limited disease have not yet been reached, and, at 11.5 months in the case of patients with extensive disease, are unexpectedly high. In comparison with combinations containing cisplatin, the present combination would appear to be superior, and its toxicity is also lower. For a definitive assessment of its usefulness, it must be compared with other standard treatment regimens in prospective, randomized studies.

Adult↗