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.

Klastersky, Jean; Sculier, Jean-Paul; Ravez, P; Libert, P; Michel, Jeffrey; Vandermoten, G; Rocmans, Pierre Arthur; Bonduelle, Y.; Mairesse, M.; Michiels, Thirsa

doi:10.1200/jco.1986.4.12.1780

Cited by 132 publications

(26 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the treatment of advanced non-small cell lung cancer Klastersky et al (1986) conducted a randomised trial comparing a high (120 mg m 2) or standard (60 mg m-2) dose of cisplatin in combination with etoposide. They reported a 25% objective response rate in the standard arm and 29% in the high dose arm with no improvement in survival.…”

Section: Dose Escalating Studiesmentioning

confidence: 99%

Dose intensity in cancer chemotherapy

Dodwell

Gurney²,

Thatcher³

1990

Br J Cancer

View full text Add to dashboard Cite

There is substantial evidence that, for the majority of antitumour agents including alkylating agents, anthracycline antibiotics and anti-metabolites, there is a steep dose response curve when these agents are studied in in vitro and in vivo models (Griswold et al., 1963;Bruce et al., 1966;Schabel et al., 1984). It is this dose-response relationship which is often cited in support of high dose chemotherapy with autologous bone marrow rescue as a promising avenue for the treatment of solid tumours. The purpose of this review is to assess the evidence that dose and dose intensity are important determinants of outcome in the treatment of human cancer with cytotoxic chemotherapy. We will review retrospective and prospective studies of dose and dose intensity in a variety of tumour types, and discuss how future clinical studies may be planned and presented to provide a more informed therapeutic rationale for exposing patients to greater doses of cytotoxic drugs in an attempt to improve outcome. Retrospective dose intensity analysis Breast cancerIn 1984 Hryniuk and Bush analysed the complete and partial remission rates and median survival times of 26 published studies using CMF-type regimens in the treatment of advanced breast cancer. For each regimen they also calculated the average relative dose intensity in the following way.The doses of cyclophosphamide, methotrexate and 5-fluorouracil were converted to a standard form of mg m2 per week. The dose intensities of each agent were compared to the dose intensity of a regimen used by Cooper (1969). The dose intensities of the test regimen were expressed as a fraction of the intensities of each drug in the Cooper protocol. The relative dose intensities for each drug in an individual CMF regimen were then averaged to give the average relative dose intensity (ARDI) of CMF-containing therapy for that particular 'test' regimen. They found a linear relationship between response rate and ARDI (Figure 1). The relationship was even more clearcut when doses actually delivered to patients, rather than planned protocol doses, were used to calculate ARDI (Figure 1).When the ARDI of a variety of CAF (cyclophosphamide, doxorubicin and 5-fluorouracil) regimens were calculated in the same way and expressed as a fraction of the ARDI of a dose intensive 'reference' regimen used by Bull and Tormey (1978) again there was a clear positive correlation between ARDI and response rate and again the relationship was clearer when delivered, rather than planned, doses were used. Hryniuk and Bush also extended their observations to median survival time. The median survival time (MST) (of all patients) and the remission rates in these studies (CMF and CAF)

show abstract

Section: Dose Escalating Studiesmentioning

confidence: 99%

Dose intensity in cancer chemotherapy

Dodwell

Gurney²,

Thatcher³

1990

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…The most active drugs so far have been cis-platinum (II) diamine dichloride (CDDP) (Loether and Einhorn, 1984), vindesine (Klastersky et al, 1983), vinblastin, mitomycin C and ifosphamide (Worrall, 1982) in the chemotherapy of nonsmall-cell lung cancer. The overall response rate is in the range 20-30% with 3-5% complete responses (Donnadieu et al, 1991).…”

mentioning

confidence: 99%

Enhancement of sensitivity of human lung adenocarcinoma cells to growth-inhibitory activity of interferon alpha by differentiation-inducing agents

Goto

Yamamoto‐Yamaguchi²,

Honma³

1996

Br J Cancer

View full text Add to dashboard Cite

Summary A low concentration of differentiation inducers such as dimethylsulphoxide (DMSO), sodium butyrate, hexamethylene bisacetamide and sodium phenylacetate greatly enhanced the antiproliferative effect in vitro and in vivo of interferon a (IFN-a) to several human lung adenocarcinoma cells. The agents induced morphological changes in the adenocarcinoma cells and the agents together with IFN-a-induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. To understand the mechanism of the DMSO-enhanced interferon sensitivity, we examined the effect of DMSO on high-affinity IFN-a receptor and interferon-stimulated promoter-binding factors. The lung adenocarcinoma cells were not impaired in IFN-a receptor and interferon-stimulated gene transactivation factor 3 (ISGF-3). Our data suggest that the enhancement of interferon sensitivity in the lung adenocarcinoma cells acts downstream of the activation of ISGF-3.Keywords: interferon; lung carcinoma; differentiation inducer; biological response modifier Lung cancer survival remains poor, with approximately 13% a 5 year survival in 1993 (Ginsberg et al., 1993). The most active drugs so far have been cis-platinum (II) diamine dichloride (CDDP) (Loether and Einhorn, 1984), vindesine (Klastersky et al., 1983), vinblastin, mitomycin C and ifosphamide (Worrall, 1982) in the chemotherapy of nonsmall-cell lung cancer. The overall response rate is in the range 20-30% with 3-5% complete responses (Donnadieu et al., 1991). The current treatment results from non-smallcell lung cancer clearly call for improved therapy.The degree of differentiation is an important prognostic factor in many tumours. Induction of differentiation is closely linked to loss of tumorigenicity, and differentiation inducers can block the phenotypic expression of malignant cells. The use of all-trans retinoic acid in the treatment of patients with acute promyelocytic leukaemia has shown that differentiation therapy can lead to a predictable clinical remission (Huang et al., 1988;Degos, 1990;Ohno et al., 1993). However, administration of differentiation inducer alone in experimental therapy of solid tumours has produced only low remission rates. Furthermore, differentiation induction of solid tumours is not always an irreversible process. These b findings call for other strategies, such as combination of differentiation induction with chemotherapy, radiotherapy and/or immunotherapy. Induction of differentiation alters the properties of leukaemia and embryonal carcinoma cells, such as sensitivities to chemotherapeutic drugs (Okabe-Kado et al., 1986;Honma et al., 1991;Okabe-Kado et al., 1991;Guchelaar et al., 1993). We previously reported that treatment with haemin, an inducer of erythroid differentiation, greatly increased the sensitivity of human myeloid leukaemia K562 cells to 1-fl-D-arabinofuranosyl cytosine (Honma et al., 1991;Okabe-Kado et al., 1986), and that erythroid differentiation factor (activin A) enhanced the sensitivity of multidrug-resistant leukaemia cells...

show abstract

“…This difference was observed in a very small group of patients (n535). The ELCWP was unable to replicate the results in a much higher number of patients [45]. High doses of cisplatin have the disadvantage of significantly higher renal, auditory and neurological toxicities [49].…”

Section: What Is the Indicated Dosage Of Cisplatin?mentioning

confidence: 95%

“…There are five randomised trials that have investigated this question (table 6), all of which were performed with old drugs [44][45][46][47][48]. None of the studies were able to report a significant advantage in favour of high doses of cisplatin (100-120 mg?m ).…”

Section: What Is the Indicated Dosage Of Cisplatin?mentioning

confidence: 99%

First- and second-line therapy for advanced nonsmall cell lung cancer

Sculier¹,

Moro-Sibilot²

2009

European Respiratory Journal

View full text Add to dashboard Cite

The objectives for the treatment of advanced nonsmall cell lung cancer are palliative and include improvement of survival, symptom control, quality of life and cost. The level of evidence of these benefits is based on multiple randomised trials and meta-analyses. Cisplatinbased chemotherapy with one of the regimens shown to be effective should be preferred. Carboplatin may be substituted for cisplatin if medical contraindications exist. Nonplatinumbased regimens are indicated as first-line treatment for advanced nonsmall cell lung cancer in patients for whom platinum-based chemotherapy is contraindicated. Single drug chemotherapy may be considered in patients with poor performance status. The choice of the active drugs depends on the patient's medical condition. There is no conclusive evidence that high doses of cisplatin (100-120 mg?m -2 ) provide better results than standard lower doses (50-60 mg?m -2 ) in terms of survival. The optimal duration of chemotherapy is poorly documented in advanced nonsmall cell lung cancer. A minimum of four to six cycles is advised in responding patients. Second-line chemotherapy is now accepted as a standard and should be offered to patients with good performance status and failing platinum-based first-line chemotherapy. Evidence is in favour of docetaxel and in the case of adenocarcinoma and adequate renal function, pemetrexed is recommended.

show abstract

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.

Cited by 132 publications

References 10 publications

Dose intensity in cancer chemotherapy

Dose intensity in cancer chemotherapy

Enhancement of sensitivity of human lung adenocarcinoma cells to growth-inhibitory activity of interferon alpha by differentiation-inducing agents

First- and second-line therapy for advanced nonsmall cell lung cancer

Contact Info

Product

Resources

About