Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer.

Ihde, Daniel C.; Mulshine, J L; Kramer, Barry; Steinberg, S. M.; Linnoila, R. Ilona; Gazdar, Adi F.; Edison, Margaret; Phelps, Ruby; Lesar, May; Phares, J C

doi:10.1200/jco.1994.12.10.2022

Cited by 235 publications

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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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confidence: 99%

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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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“…1,[15][16][17][18][19] To administer this three-drug combination safely, doses of all three drugs were reduced compared with the doses feasible in various two-drug combinations. Even with the routine use of granulocyte-colony stimulating factor (G-CSF), our previous Phase I trial demonstrated that dose-limiting thrombocytopenia prevented meaningful dose escalation.…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung carcinoma

Hainsworth¹,

Morrissey²,

Scullin³

et al. 2002

Cancer

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“…Several studies have failed to demonstrate any major improvement in median survival [52][53][54]. However, a recent study in limited SCLC demonstrated that a 20% higher initial dosage of cyclophosphamide and cisplatin achieved a 25% increase in complete remission rate, a 50% increase in the duration of complete remission and a better 2 year survival rate (p=0.016) [42].…”

Section: Intensification Of Chemotherapy With Csfsmentioning

confidence: 99%

Colony-stimulating factors as an adjunct to chemotherapy in small cell lung cancer

Urban

Schüller²,

Lebeau³

1996

Eur Respir J

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Myelosuppression is the major dose-limiting toxicity of chemotherapy in small cell lung cancer (SCLC). The capacity of colony stimulating factors (CSFs) to stimulate granular neutrophil recovery may be of great value to prevent or cure febrile neutropenia and to increase dose-intensity. The aim of this review was to assess the current use of CSFs in SCLC on the basis of experimental and clinical data.Primary CSF administration has been shown to reduce the incidence of febrile neutropenia, hospital admission rate, and antibiotic use subsequent to cyclophosphamidedoxorubicin-high dose etoposide (CDE) chemotherapy, without improvement of survival or disease control. Primary CSF administration may be recommended when the expected incidence of febrile neutropenia is at least 40%. This benefit has not been established with less myelosuppressive regimens, such as cisplatin-etoposide (PE), which remains an alternative combination in SCLC when standard doses are used. A trial comparing high-dose CDE + CSF with PE would be of considerable interest.There is currently little clinical basis for the use of CSFs to increase chemotherapy dose-intensity, outside clinical trials. Peripheral blood progenitor cells mobilized with CSFs offer interesting prospects. Further studies, with later initiation, shorter duration or lower doses of CSFs, are warranted to improve the cost-effectiveness of CSFs.CSF therapy in addition to antibiotics is normally not justified in febrile neutropenia, except perhaps in selected patients with sepsis syndromes, hypotension or pneumonia.

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Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer.

Abstract: No therapeutic benefits resulted from increasing planned doses by 67% for the first two cycles of EP in patients with extensive-stage SCLC. Higher doses were associated with substantially worse toxicities.

Cited by 235 publications

References 0 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

Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung carcinoma

Colony-stimulating factors as an adjunct to chemotherapy in small cell lung cancer

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