Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial.

Maksymiuk, Andrew W.; Jett, James R.; Earle, John D.; Su, Jian-An; Diegert, F A; Mailliard, James A.; Kardinal, Carl G.; Krook, James E.; Veeder, Michael H.; Wiesenfeld, Martin

doi:10.1200/jco.1994.12.1.70

Cited by 64 publications

(27 citation statements)

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“…Among the active drugs in SCLC, cyclophosphamide-adriamycin-vincristine (Fukuoka et al, 1986; Feld et al, 1989) or cyclophosphamide-adriamycin-etoposide combinations have long been known as having a good efficacy/toxicity ratio. Other combination chemotherapies such as cisplatin and etoposide have been tested successfully and have given encouraging results in terms of both response and survival rates (Ihde et al, 1984;Maksymiuk et al, 1994; Evans et al, 1985). It rapidly appeared that response to chemotherapy is one of the most important factors for SCLC patients to achieve long-term survival (Osterlind et al, 1986) in association with other known favourable prognostic factors, namely limited disease, good performance status, lower age group, low serum lactate dehydrogenase, low alkaline phosphatases and normal serum sodium and bicarbonate (Cerny et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…Various drug combinations have been used in sequential chemotherapies in order to improve both response rate and survival. Among these combinations, cisplatin and etoposide (Ihde et al, 1984;Maksymiuk et al, 1994;Evans et al, 1985) or cyclophosphamide, doxorubicin and vincritine (Feld et al, 1989) are two widely applied regimens inducing a 80-90% overall response rate including a 30-40% complete response rate. Despite the high chemosensitivity of SCLC, the 2-and 5-year survivals are low due to the frequent occurrence of chemoresistant relapses after these classical regimens.…”

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Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent

2000

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Summary Chemotherapy is the backbone of small-cell lung cancer therapy. However, optimal drug combinations and schedules remain to be defined and there is hitherto no world-wide accepted standard regimen. Cisplatin, an alkylating agent with high putative toxicity is currently widely used although its effectiveness in this disease has not been established firmly. We conducted a meta-analysis of published data reporting trials randomizing a cisplatin-containing regimen versus a regimen without this alkylating agent in order to determine possible differences in survival response and toxicity. Nineteen trials have been identified in medical literature (4054 evaluable patients). Ten trials randomized patients to receive a cisplatin-etoposide regimen versus a regimen without any of these two drugs. A subgroup analysis was, therefore, carried out in the nine remaining trials that randomly allocated patients between two regimens differing in the absence or presence of cisplatin, whereas etoposide was given (or not given) in both arms (1579 evaluable patients). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death and the increase in probability of being responders to chemotherapy. There was no significant difference between the cisplatin-containing regimen and the regimen without this drug when the risk of toxic-death was taken into account with respective probabilities of 3.1 and 2.7% (NS). Patients randomized in a cisplatin-containing regimen had an increase in probability of being responders with an OR of 1.35, 95% confidence interval (CI) of 1.18-1.55; P < 10 -5 corresponding to an increase of objective (partial plus complete) response rate from 0.62 to 0.69 (a result taking into account a significant heterogeneity). Patients treated with a cisplatin-containing regimen benefited from a significant reduction of risk of death at 6 months and 1 year with respective OR 0.87, 95% CI 0.75-0.98, P = 0.03, and or 0.80, 95% CI 0.69-0.93, P = 0.002 (no statistical heterogeneity). This corresponded to a significant increase in the probability of survival of 2.6% and 4.4% at 6 months and 1 year respectively. The meta-analysis restricted to the subset of nine trials without etoposide treatment imbalance reached similar conclusions. A cisplatin-containing regimen yields a higher response rate and probability of survival than does a chemotherapy containing others alkylating agents without a perceptible increase in risk of toxic-death. (2000) 83(1), 8-15 © 2000 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1164, available online at http://www.idealibrary.com on *Present address: Cliniques Universitaires UCL de Mont-Godinne, B 5530 Yvoir, Belgium combination versus radiotherapy alone has demonstrated that the combined modality treatment reduces the risk of death. This effect is particularly apparent where the chemotherapy is based on a modern combination. It is noteworthy that the break between older ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent

2000

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“…7 Although the results of this trial were good, with a response rate of 77% and a median survival of 10.5 months, they were similar to the results reported in prior NCCTG trials and in other cooperative group trials. 1,2,18,19 In 1994, the NCCTG reported on the treatment of Ͼ 200 patients with extensive-stage SCLC using four different schedules and sequences of etoposide and cisplatin, resulting in a median survival of 9.5-11.1 months and a 2-year survival rate of 4 -12%. 1 Shaw et al reviewed the NCCTG and Mayo Clinic data base of patients enrolled in Phase II-III trials from 1975 to 1990.…”

Section: Discussionmentioning

confidence: 99%

“…1,2,18,19 In 1994, the NCCTG reported on the treatment of Ͼ 200 patients with extensive-stage SCLC using four different schedules and sequences of etoposide and cisplatin, resulting in a median survival of 9.5-11.1 months and a 2-year survival rate of 4 -12%. 1 Shaw et al reviewed the NCCTG and Mayo Clinic data base of patients enrolled in Phase II-III trials from 1975 to 1990. For Ͼ 800 patients with extensivestage SCLC who were treated on protocols during that period, the median survival was 9.3 months, and the 2-year survival rate was 2%.…”

Section: Discussionmentioning

confidence: 99%

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Alternating chemotherapy with etoposide plus cisplatin and topotecan plus paclitaxel in patients with untreated, extensive‐stage small cell lung carcinoma

Jett

Hatfield

Hillman

et al. 2003

Cancer

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BACKGROUNDThe objective of this study was to test the response rate and toxicity of alternating chemotherapy in previously untreated patients with extensive‐stage small cell lung carcinoma (SCLC).METHODSPatients with histologically proven, extensive‐stage SCLC, with a performance status of 0–2, and who had received no prior chemotherapy were eligible. The design was a two‐stage, Phase II, multicenter trial. Treatment consisted of alternating chemotherapy every 3 weeks with etoposide (100 mg/m2 on Days 1–3) and cisplatin (30 mg/m2 on Days 1–3) on Cycles 1, 3, 5 and with topotecan (1 mg/m2 on Days 1–5) and paclitaxel (200 mg/m2 on Day 5) on Cycles 2, 4, and 6. Filgrastim support was given with Cycles 2, 4, 6.RESULTSForty‐four patients were eligible and evaluable. The primary toxicity was myelosuppression. The median absolute neutrophil count was 300/μL with 70% Grade 4 neutropenia. The median platelet count was 58,000/μL with 23% Grade 4 thrombocytopenia. Grade 4 nonhematologic toxicities occurred in 16% of patients. Overall toxicities were not different between the two regimens. There were no treatment‐related deaths. Complete or partial responses occurred in 34 patients (77%). The median time to progression was 6.9 months, with a median survival of 10.5 months and with 1‐year and 2‐year survival rates of 37% and 12%, respectively.CONCLUSIONSThe regimen of alternating chemotherapy was associated with substantial myelosuppression and resulted in a high response rate and good overall survival. The results were similar to those reported in prior trials and did not suggest any improvement in therapy for patients with SCLC. Cancer 2003;10:2498–503. © 2003 American Cancer Society.DOI 10.1002/cncr.11377

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Laplace regression with censored data

2010

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We consider a regression model where the error term is assumed to follow a type of asymmetric Laplace distribution. We explore its use in the estimation of conditional quantiles of a continuous outcome variable given a set of covariates in the presence of random censoring. Censoring may depend on covariates. Estimation of the regression coefficients is carried out by maximizing a non-differentiable likelihood function. In the scenarios considered in a simulation study, the Laplace estimator showed correct coverage and shorter computation time than the alternative methods considered, some of which occasionally failed to converge. We illustrate the use of Laplace regression with an application to survival time in patients with small cell lung cancer.

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Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial.

Abstract: The bolus administration of EP with E following P for the first two cycles of chemotherapy was the most effective regimen, with especially encouraging survival for LD patients.

Cited by 64 publications

References 26 publications

Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent

Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent

Alternating chemotherapy with etoposide plus cisplatin and topotecan plus paclitaxel in patients with untreated, extensive‐stage small cell lung carcinoma

Laplace regression with censored data

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