Cooperative Group Research Endeavors in Small-cell Lung Cancer: Current and Future Directions

Current and Future Directions

Randeep Sangha; Primo N. Lara, Jr.; Alex A. Adjei; Paul Baas; Hak Choy; Laurie E. Gaspar; Glenwood Goss; Nagahiro Saijo; Joan H. Schiller; Everett E. Vokes; David R. Gandara

Disclosures

Clin Lung Cancer. 2009;10(5) 

In This Article

European Organization for the Research and Treatment of Cancer

The EORTC extends over multiple European countries and is a key contributor to clinical lung cancer research. Building upon the Intergroup 0096 study in LS-SCLC, the CONVERT (Concurrent ONce-daily VErsus Radiotherapy Twice-daily) trial hypothesizes that increasing the total dose of once-daily thoracic irradiation will improve efficacy and negate the benefit of twice-daily fractionation, thus making the once-daily regimen more practical and logistically easier to deliver. The CONVERT trial is a 2-arm, multicenter, randomized phase III Intergroup trial comparing a once-daily with a twice-daily schedule, given concurrently with cisplatin and etoposide (Figure 2). The radiation therapy regimen put forth by the Intergroup 0096 trial (45 Gy, twice-daily fractionation over 3 weeks) will be compared with 66 Gy, once-daily fractionation over 6.5 weeks. Unlike in the CALGB 30610 trial, thoracic irradiation will commence with the second cycle of chemotherapy. The primary endpoint will be OS, and the goal for accrual is 532 patients within a 4-year time span. The study is currently open in a number of EORTC member institutions.

Figure 2.

Treatment Schema: Phase III CONVERT Trial
aMaximum of 6 cycles of cisplatin/etoposide.
Abbreviations: CONVERT = Concurrent ONce-daily VErsus Radiotherapy Twice-daily; CR = complete response; D = day; fr = fractions; OS = overall survival; PCI = prophylactic cranial irradiation; PD = progressive disease; PFS = progression-free survival; PR = partial response; RT = radiation therapy; SD = stable disease

Amrubicin is a novel cytotoxic agent being evaluated for the treatment of patients with ES-SCLC. It is a completely synthetic 9-amino-anthracycline that is converted to its 13C alcohol metabolite amrubicinol, which has greater antitumor activity than its parent molecule, in stark contrast to the traditional anthracycline derivatives, doxorubicinol and daunorubicinol.[31] Moreover, amrubicin has been found to be less cardiotoxic than doxorubicin in animal models.[33] In a study of patients with refractory and sensitive relapsed SCLC, amrubicin has shown activity as a single agent. The overall response rate (ORR) was approximately 50% in each group, and the median PFS, median OS, and 1-year survival times in the refractory and sensitive groups were 2.6 months and 4.4 months, 10.3 months and 11.6 months, and 40% and 46%, respectively.[34] EORTC 08062 is a phase II trial equally randomizing chemotherapy-naive patients with ES-SCLC to 1 of 3 treatment arms: arm 1, amrubicin 45 mg/m2 on days 1–3; arm 2, amrubicin 40 mg/m2 on days 1–3 plus cisplatin 60 mg/m2 on day 1; and arm 3, cisplatin 75 mg/m2 on day 1 plus etoposide 100 mg/m2 I.V. on day 1 followed by oral etoposide 200 mg/m2 on days 2 and 3. In all arms, treatment is repeated every 21 days in the absence of progressive disease or unacceptable toxicity. Patients are stratified based on institution, sex, and performance status. The primary endpoint is RR, with secondary endpoints examining PFS, OS, and toxicity. Amrubicin is already approved in Japan and is currently being investigated in the United States in a multinational, randomized phase III trial for patients with SCLC who do not respond to first-line therapy. Considerable hope exists for this agent, but its role will need to be more clearly defined.

Finally, a proposal is in place for a phase II EORTC 08061 trial treating patients with chemotherapy-naive or sensitive relapsed ES-SCLC. Sunitinib will be given as a single oral agent (150-mg loading dose followed by 37.5 mg daily) until progressive disease. Disease control rate at 4 weeks after the start of treatment will be the primary endpoint.

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