Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group.

Gandara, David R.; Crowley, John; Livingston, Robert B.; Perez, Edith A.; Taylor, Charles W.; Weiss, G B; Neefe, John R.; Hutchins, Laura F.; Roach, Ralph W.; Grunberg, Steven M.

doi:10.1200/jco.1993.11.5.873

Cited by 139 publications

(45 citation statements)

References 23 publications

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“…10 randomized trials comparing a basic chemotherapy regimen with or without MMC (Einhorn et al, 1986;Crino et al, 1988Crino et al, , 1990Bonomi et al, 1989, Luedke et al, 1990Fukuoka et al, 1991;Shinkai et al, 1991;Weick et al, 1991;Mylonakis et al, 1992;Gandara et al, 1993;Masutani et al, 1996) were available for a metaanalysis. Their main characteristics and results are summarized in Table 2 8 of them included more than 2 arms but we considered only the 2 arms of interest, leading to a total of 1769 eligible patients, 876 treated in the experimental arm with MMC and 893 in the control arm without MMC.…”

Section: Question 2: Does MMC Improve the Results When Added To Othermentioning

confidence: 99%

“…Einhorn, 1986Crino, 1988-90 Bonomi, 1990Luedke, 1990Fukuoka, 1991Shinkai, 1991Weick, 1991Mylonakis, 1992 Gandara, 1993 Crino, 1988−90 Bonomi, 1990Luedke, 1990Fukuoka, 1991Shinkai, 1991Weick, 1991Mylonakis, 1992Gandara, 1993Masutani, 1996 OVERALL 0.0 1.3 2.5 3.75 5.0 On the 4 prospective phase II trials found in the literature (Table 4), 3 deal with a combination of MMC with vindesine (Kris et al, 1985;Sculier et al, 1986, Bonomi et al, 1989) and 1 with cisplatin and vinblastine (Gridelli et al, 1992). The ELCWP quality score for phase II trials ranged from 21.1% to 75% with a median of 61.1%.…”

Section: Question 2: Does MMC Improve the Results When Added To Othermentioning

confidence: 99%

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The role of mitomycin in the treatment of non-small cell lung cancer: a systematic review with meta-analysis of the literature

Sculier¹,

Ghisdal²,

Berghmans³

et al. 2001

Br J Cancer

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In the 1990s, chemotherapy has been shown able to improve survival of patients presenting with advanced non-small cell lung cancer (NSCLC, 1995). The survival benefit was obtained with first-generation active cytostatic agents -mainly ifosfamide, vinblastine, vindesine, mitomycin (MMC) -in combination with cisplatin (Donnadieu et al, 1991). New active drugs -the second generation -have appeared during the last decade, including gemcitabine, paclitaxel, docetaxel, vinorelbine and irinotecan. Their role in addition or in place of the first-generation agents, which should not be considered as obsolete for the unique reason that they are older and less fashionable, has yet to be defined (Meert et al, 1999).In this context, we have performed a systemic review of the literature about the role of one of the first-generation drugs, mitomycin (MMC), in the management of NSCLC. In order to determine if it is worthy to further conduct trials with that agent, we have searched answers to the 3 following questions: (1) is MMC an active drug against NSCLC? (2) does MMC improve the results when added to other active agents? (3) is MMC useful for salvage therapy? We have performed this investigation by using a methodology similar to that we have already used to conduct evidencebased medicine analyses of the literature. MATERIAL AND METHODSTo be eligible for the systematic review, a trial had to fulfil the following criteria: to deal only with NSCLC, to have been published as a full paper in the English or French language, to have a prospective design and to assess the effect of MMC in a randomized trial or in a first-line or second-line phase II trial according to the studied question.Trials were identified by an electronic search (Medline) in addition to the use of the personal bibliography of one of the authors and by consulting the references reported in the selected articles.Each trial was read and assessed for methodology by 12 investigators, including 11 physicians and 1 biostatistician. Each investigator independently extracted the data from the articles and disagreements were resolved by consensus. Randomized trials were evaluated for methodology by 2 quality scores calculated on the basis of the data reported in the publications: the score proposed by Chalmers et al (1981) and used by Marino in two meta-analyses (Marino et al, 1994(Marino et al, , 1995; and the score proposed by the ELCWP (European Lung Cancer Working Party) (Mascaux et al, 2000). Phase II trials were assessed by the ELCWP score for phase II studies (Meert et al, 1999).The result of a phase III trial was considered as conclusive if the P value for the statistical test comparing the survival distributions between arms for the overall patients populations was <0.05 in favour of the experimental arm. The trial was then called 'positive'. In the other situations (statistically significant survival benefit for the control arm or non-statistically significant difference in survival distributions), it was called 'negative'.The association between the quality s...

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Section: Question 2: Does MMC Improve the Results When Added To Othermentioning

confidence: 99%

Section: Question 2: Does MMC Improve the Results When Added To Othermentioning

confidence: 99%

The role of mitomycin in the treatment of non-small cell lung cancer: a systematic review with meta-analysis of the literature

Sculier¹,

Ghisdal²,

Berghmans³

et al. 2001

Br J Cancer

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“…Cisplatin has been used in combinations with other different chemotherapeutic agents, such as DNA-alkylators, topoisomerase II inhibitors, vinorelbine and gemcitabine (Fukuoka et al, 1992;Liu, 1993;Sculier et al, 1994;Gridelli et al, 1996;Wozniak et al, 1998;Lippe et al, 1999). Besides evaluation of different combinations of cisplatin, important other approaches have focused on increasing the dose and/or the dose intensity of the drug using higher doses per course (Klastersky et al, 1986;Gandara et al, 1993), or shortening the treatment interval (Planting et al, 1993(Planting et al, , 1994(Planting et al, , 1995a(Planting et al, , b, 1996a(Planting et al, , b, 1997(Planting et al, , 1999. Cisplatin when applied as a single agent at a 3-or 4-weekly schedule and a dose of 100 mg m À2 has a low activity in advanced NSCLC and the overall response rate (RR) varies from 12 to 15% (Gandara et al, 1993;Wozniak et al, 1999).…”

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confidence: 99%

Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancer

et al. 2003

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The objective of this phase II and pharmacologic study was to explore the feasibility, toxicity and activity of adaptive intrapatient dose escalation of cisplatin in a dose-intensive weekly schedule using predefined levels of exposure, with the ultimate aim to improve the antitumour activity of the therapy in patients with nonsmall cell lung cancer (NSCLC). Platinum DNA-adduct levels in peripheral white blood cells during treatment were used as the primary parameter for adaptive dosing. If DNA-adduct levels were not available, the area under the concentration -time curve (AUC) of unbound platinum in plasma was used for dose adaptation. Target levels for DNA-adducts and AUC have been defined in a previously performed pharmacologic study. The feasibility of adaptive dosing was tested in 76 patients with stage IIIB and IV NSCLC, who were planned to receive 6 weekly courses of cisplatin at a starting dose of 70 mg m À2 , together with daily low oral dose of 50 mg VP16. In total, 37 patients (49%) who were given more than one course received a dose increase varying from 10 to 55%. The majority of patients reached the defined target levels by a dose increase during course two. Relevant grade 2 neurotoxicity was observed in eight (10%) patients and reversible ototoxicity grade 2 in 14 (18%) patients. The strategy of adaptive intrapatient dose adjustment of cisplatin is practically feasible in a research setting even when results for dose adaptation have to be reported within a short time-period of 1 week. The toxicity appeared to be manageable in this cohort of patients. In some patients, exposure after the standard dose was substantially lower than the defined target level and significant dose escalations of more than 50% had to be applied. The response rate (RR) was relatively high: overall 40% (29 out of 72 patients) partial remission (PR), in patients with stage IIIB the RR was 60% (15 out of 25 patients) and with stage IV 30% (14 out of 47 patients). Randomised studies are needed to determine whether the adaptive dosing strategy results in better efficacy than standard dosing.

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“…The use of higher cisplatin doses was based on one small randomized trial that demonstrated longer duration of response and a survival advantage for responders in the higher dose arm, but no overall survival results were reported (Gralla et al, 1981). However, three subsequent larger randomized studies have failed to show advantage for the higher cisplatin doses, and toxicity was considerably worse (Klastersky et al, 1986;Gandara, 1993;Felip et al, 1997).The first randomized study using new agents compared vinorelbine/cisplatin to vindesine/cisplatin to vinorelbine alone in 612 patients. The vinorelbine/cisplatin combination resulted in a significantly superior response rate (30% vs 19% vs 14%), survival (median survival in weeks 40 vs 32 vs 31) and 1-year survival (35% vs 27% vs 30%) (Le Chevalier et al, 1996).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Where to go with new expensive treatments in NSCLC

Webb

O’Brien²

1998

Br J Cancer

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This month's journal reports two studies using the combination of irinotecan and cisplatin in advanced non-small-cell lung cancer. The first is a phase II study that achieves a high response rate of 54%, with 33% of patients alive at 1 year (Masuda et al, 1998). The second is a phase I dose-finding study of the same combination but given with concomitant radiotherapy in locally advanced disease. The initial doses chosen were of the order of 40% of the usual irinotecan weekly dose with 60 mg m-2 cisplatin. This chemoradiotherapy combination was not tolerated because of a number of toxicities, but in particular leucopenia. The study was stopped early but even at these low doses, a response rate of 67% was obtained (Yokoyama et al, 1998). This has important implications for the use of irinotecan with radiotherapy in both lung and bowel cancer (Yokoyama et al, 1998).Where do we take these new treatments and how do we make progress in the treatment of non-small-cell lung cancer? We now have five new drugs with activity in non-small-cell lung cancer and all of them priced in the range of between 6 and 30 times the cost of any of our previous regimens. This compounds the problem in non-small-cell lung cancer when the last new drug in the late 1980s, vinorelbine, has yet to be tested or accepted as standard treatment in this country. Currently, drug budgets are stretched to meet the increasing expenditure with our current 'cheap' regimens, never mind addressing new expensive treatments. It is a shame that we have come to the point when new treatments are not being hailed into clinical trials with enthusiasm and optimism, as currently there are no prospects that these new agents, if better, can then become standard treatments.Gemcitabine, the taxanes (paclitaxel, docetaxel), the topoisomerase I inhibitors (irinotecan, topotecan) and vinorelbine all have significant single-agent activity with response rates of at least 20% and encouraging survival data with acceptable toxicities (Table 1). There have now been numerous phase II studies investigating these agents in combination with platinum compounds, including the two in this issue. They have shown promising activity with relatively high response rates and 1-year survivals of 40% or more (Table 2). However, although promising, these phase II studies must be viewed with caution, and judgment must be reserved until the results of phase III randomized studies comparing these combinations to standard treatments become available.The commonest (standard) treatments for non-small-cell lung cancer in this country are cisplatin based, usually MVP (mitomycin, vinblastine and cisplatin) or MIC (mitomycin, ifosfamide and Received 15 May 1997 Accepted 15 May 1997 Correspondence to: MER O'Brien cisplatin), with cisplatin used at a dose of around 50 mg m-2. This differs to the USA where the cisplatin dose is usually higher and the combinations most frequently used are etoposide/cisplatin and vinblastine/cisplatin. The only randomized study comparing MIC, MVP (both using higher-dose cis...

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Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group.

Cited by 139 publications

References 23 publications

The role of mitomycin in the treatment of non-small cell lung cancer: a systematic review with meta-analysis of the literature

The role of mitomycin in the treatment of non-small cell lung cancer: a systematic review with meta-analysis of the literature

Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancer

Where to go with new expensive treatments in NSCLC

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