Randomised phase II study of cisplatin-etoposide versus infusional carboplatin in advanced non-small-cell lung cancer and mesothelioma

Our plain-English summary of Randomised phase II study of cisplatin-etoposide versus infusional carboplatin in advanced non-small-cell lung cancer and mesothelioma, by S.C. White, H. Anderson, G.C. Jayson, et al (Annals of Oncology, 2000).

The study

• Authors: S.C. White, H. Anderson, G.C. Jayson, L. Ashcroft, M. Ranson, N. Thatcher
• Journal: Annals of Oncology
• Published: 2000;11(2):201-6
• Type of article: Randomized trial
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: A randomised phase II study was performed to compare standard combination chemotherapy containing cisplatin and etoposide with infusional carboplatin.

Patients And Methods: One hundred twenty patients with locally advanced/metastatic non-small-cell lung cancer or mesothelioma were enrolled. All were chemotherapy-naïve and had a Karnofsky performance status of > or = 50. Patients were randomised to either four cycles of bolus therapy of cisplatin 80 mg/m2 day 1, etoposide 120 mg/m2 day 1-3, or continuous infusion of carboplatin 100/mg/m2/week for six weeks.

Results: No patients on infusional therapy incurred grade 3-4 toxicity while in the bolus arm, grade 3 and grade 4 leucopenia occurred in 17% and 35% of patients, respectively. Grade 4 thrombocytopenia occurred in 8% of patients and there were two instances of grade 3 renal toxicity. No responses occurred in the pump arm. Eight of forty-six patients with non-small-cell lung cancer responded to treatment (response rate 17.3%) with two complete responses and six partial responses. Only one patient with mesothelioma responded to bolus therapy. There was no difference in survival for the subset of NSCLC patients. Survival for mesothelioma patients in the pump arm was superior but this was likely to be a result of early deaths in the bolus arm.

Conclusions: The pump arm was well-tolerated but not active, whilst combination platinum-based therapy demonstrated activity but significantly more toxicity than the pump arm. Further studies of infusional carboplatin with this schedule are not warranted.

In plain English

This randomised phase II chemotherapy trial did not study asbestos exposure. Between 1994 and 1997, 120 patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) or mesothelioma, none previously given chemotherapy, were randomised, 60 per arm. One arm was scheduled to receive four three-weekly cycles of bolus cisplatin and etoposide; the other, six weeks of continuous pump-infused carboplatin at 100 mg/m2 per week. Twenty-five patients had mesothelioma. In the bolus arm, grade 3 leucopenia occurred in 17% of patients and grade 4 in 35%. The pump arm had no significant leucopenia or thrombocytopenia. Among NSCLC patients, 8 of 46 in the bolus arm responded (17.3%, 95% confidence interval 7.8 to 31.4); none of the 43 pump patients with response data had a complete or partial response. NSCLC survival did not differ significantly between the arms. In mesothelioma, one bolus patient had a partial response. Mesothelioma survival significantly favoured the pump (median 21.7 versus 18.7 weeks), which the authors said was heavily influenced by 5 of 13 early bolus-arm deaths. The authors concluded that further study of this infusional schedule was not warranted.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: randomised phase II clinical trial comparing two chemotherapy regimens; primary endpoints were toxicity and response rate
• Who was studied: 120 chemotherapy-naive patients with locally advanced (stage IIIB) or metastatic NSCLC, or biopsy-confirmed mesothelioma, enrolled 1994 to 1997 by the Department of Medical Oncology, Christie Hospital, Manchester, UK; 60 randomised to each arm; 25 had mesothelioma (13 bolus, 12 pump) and 46 per arm had NSCLC
• Exposure: No asbestos exposure was studied. The planned treatments were bolus cisplatin 80 mg/m2 on day 1 plus etoposide 120 mg/m2 on days 1 to 3, every three weeks for four cycles, versus continuous pump infusion of carboplatin 100 mg/m2 per week for six weeks
• Main results:
  • Treatment completed: in the bolus arm 24 patients (41%) received all 4 cycles (median 3 cycles); in the pump arm 67% received the full six weeks
  • Bolus arm: grade 3 to 4 anemia in nine patients (15%); grade 3 leucopenia in 17% and grade 4 in 35%. Pump arm: only two instances of grade 3 to 4 anemia and no significant leucopenia or thrombocytopenia
  • Fever with grade 3 or 4 leukopenia occurred in 14 (30.4%) of bolus-arm patients
  • NSCLC, bolus arm: response rate 17.3% (95% CI 7.8 to 31.4), with 8 of 46 patients responding, 2 of them complete responses
  • NSCLC, pump arm: 43 of 46 patients had response data; no complete or partial responses were observed; minor responses occurred in three patients; disease stabilisation occurred in 51%
  • Mesothelioma: one partial response and one minor response in the bolus arm, compared with one minor response in the pump arm (P = 0.97)
  • NSCLC survival: median 22.3 weeks in the bolus arm and 21.7 weeks in the pump arm, with no significant difference (P = 0.079); one-year survival 23.9% bolus and 13% pump
  • Mesothelioma survival: the authors reported a statistically significant advantage for the pump arm, with median 21.7 weeks versus 18.7 weeks in the bolus arm (P printed as 0.0135); no bolus patient survived more than one year, versus 33% one-year survival in the pump arm. The authors stated this was heavily influenced by 5 of 13 (38%) early deaths in the bolus arm
• The authors' conclusion: The authors concluded that single-agent infusional carboplatin at this schedule could not be recommended for inoperable NSCLC and that further studies with infusional carboplatin were not warranted
• Limitations the authors state:
  • The study was not powered to evaluate survival, and the authors thought too few patients was the more likely explanation for the similar NSCLC survival in the two arms
  • The number of mesothelioma patients was small
  • Patient acceptability of carrying a pump was not assessed

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Cisplatin, Carboplatin, Lung Cancer, Mesothelioma, Chemotherapy, Performance Status.

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