wait a moment

Treatment of Stage IIIA Non-small Cell Lung Cancer: CALGB

Treatment of Stage IIIA Non-small Cell Lung Cancer: CALGBIn general, trials using platinum-containing chemotherapy regimens in combination with radiotherapy have shown good tumor response rates and have suggested an improvement in survival. One promising pilot trial showed significantly improved median and 2-year survivals of 16 months and 30%, respectively, using four cycles of etoposide and cisplatin with concurrent radiotherapy to 60 Gy. Looking at collective data from multiple phase II trials, acute and late toxicities associated with combined chemotherapy and radiotherapy have included mild-to-severe esophagitis, pneumonitis, and also treatment-related deaths. Overall, however, these trials showed the feasibility of combined modality therapy and suggested that chemotherapy plus radiotherapy would yield improved outcomes compared to radiotherapy alone.
Multiple phase III trials using platinum chemotherapy plus radiotherapy have confirmed improved survivals for chemotherapy plus radiotherapy compared to radiotherapy alone. Selected key trials are outlined in Table 6, with some trials discussed below. Of note, the earliest trial results were negative, showing no survival benefit with chemotherapy but the regimens used had either low-dose cisplatin or non-platinum-based chemotherapy, which might be expected to be ineffective. Later trials using more appropriate dose chemotherapy all had positive results. fully

A pivotal Cancer and Leukemia Group B (CALGB) randomized trial initially presented in 1990 showed the benefit of adding chemotherapy in a sequential fashion to radiotherapy in the setting of locally advanced disease. The CALGB study compared two cycles of cisplatin and vinblastine added to standard fractionation radiotherapy to 60 Gy with radiotherapy alone in patients with favorable prognostic characteristics (good performance status and minimal weight loss). Objective tumor response rate was improved for the chemotherapy-plus-radiother-apy group compared to radiotherapy alone (56% vs 43%, p = 0.012), and survival at 2 years and 5 years was also improved (26% and 13% vs 13% and 6%, respectively).
Table 6—Randomized Controlled Trials of Sequential or Concurrent Chemoradiotherapy vs Radiotherapy Alone for Unresectable Stage III NSCLC

Source Year Patients,No. TimingChemotherapy/Radiotherapy Chemotherapy/RadiotherapyRegimens Study Result Acute Toxicity Chemotherapy Plus Radiotherapy/ Radiotherapy, % 2-year Survival Chemotherapy Plus Radiotherapy/ Radiotherapy, %
Soresi et al 19SS 95 Concurrent Cisplatin/50 Gy Negative 40/25
Mattson et al 19SS 238 Sequential plus concurrent Cyclophosphamide doxorubicin cisplatin/55 Gy Negative 19/17
Ansari et al 1991 183 Concurrent Cisplatin/60 Gy Negative 15/9
Morton et al 1991 114 Sequential MACC/60 Gy Negative 21/9 21/16
Trovo et al 1992 173 Concurrent Cisplatin/45 Gy Negative 15/7 13/13
Schaake-Koning et al 1992 308 Concurrent Cisplatin/55 Gy (split course) Positive 41/11 26/13
Wolf et al 1994 85 Sequential plus concurrent Vindesine-ifosphamide-cisplatin/50 Gy Positive 8.2/11 24/12
Le Chevalier et al 1994 353 Sequential Vindesine-loumustine-cisplatin-cyclophosphamide/65 Gy Positive 21/14
Sause et al 1995 452 Sequential Cisplatin-vinblastine/60 Gy Positive 26/22 30/19
Dillman et al 1996 155 Sequential Cisplatin-vinblastine/60 Gy Positive 14/6 26/13
Jeremic et al 1996 131 Concurrent Carboplatin-etoposide/69.9 Gy bid Positive 52/38
Cullen et al 1999 446 Sequential Mitomycin-ifosphamide-cisplatin/median 50 Gy Negative 20/16 (p = 0.14)