Preliminary report of locally advanced multimodality protocol (LAMP): ACR 427: a randomized phase II study of three chemo-radiation regimens with paclitaxel, carboplatin, and thoracic radiation (TRT) for patients with locally advanced non small cell lung cancer (LA-NSCLC)

Reviewer: Ryan Smith, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 18, 2002

Presenter: H. Choy
Presenter's Affiliation: ACR
Type of Session: Scientific

Background

The majority of NSCLC patients present with inoperable disease. Therefore, the definitive treatment is with a combination of chemotherapy (most notably platinum containing regimens) and radiation therapy. It has been shown that chemoradiation is more efficacious than radiation alone, and there is further evidence that concurrent chemoradiation is preferable to sequential chemoradiation. This study continues the investigation of the optimal timing of chemotherapy with radiation with three treatment arms: sequential, induction/concurrent, and concurrent/adjuvant.

Materials and Methods

276 patients with stage IIIA or IIIB NSCLC with KPS 70-100 and weight loss <10%
All patients were treated with carboplatin (C) and paclitaxel (P) chemotherapy with thoracic radiation therapy (TRT)
Arm 1 (Sequential): 2 cycles of P(200mg/m2) and C (AUC 6) followed by TRT (63 Gy)
Arm 2 (Induction/Concurrent): 2 cycles of induction CP chemotherapy followed by weekly P (45 mg/m2) and C (AUC 2) chemotherapy with TRT (63 Gy/34 fxs/7wks)
Arm 3 (Concurrent/Adjuvant): Concurrent CP chemotherapy with TRT followed by 2 cycles of P (200 mg/m2) and C (AUC 6)

Results

Arm 1(SEQ)(N=92), Arm 2 (IND/CON)(N=74), Arm 3 (CON/ADJ)(N=92) were well balanced with respect to age, sex, KPS, weight loss
25-30% had KPS 70-80, appoximately 2/3 were stage IIIB
Esophagitis was the main toxicity, with Grade 3/4 toxicity: Arm 1-3%, Arm 2-19%, Arm 3-28%
Completion of chemotherapy: Arm 1-96% of patients received all chemotherapy. Arm 2-46% received all 7 cycles of chemotherapy. Arm 3-67% received all cycles of chemotherapy.
MST: Arm 1-13 mo; Arm 2-13 mo; Arm 3-16.1 mo
2yr survival: Arm 1-31%; Arm 2-22%; Arm 3-33%

Author's Conclusions

Arm 3 appears to be the best arm in terms of outcome. However, in this phase IIR study, a direct correlation cannot be done
Compares favorably to RTOG reference survival guide data for sequential chemoXRT with a MST of 14.5 mo
This supports the use of concurrent chemoradiation as the control arm for future studies

Clinical/Scientific Implications

As stated above, the progression of care in inoperable NSCLC has been the addition of chemotherapy to radiation and now, the use of concurrent chemoradiation. This concurrent regimen has been supported in the past by the study by Furuse (ASCO 2000), RTOG 94-10, and the GLOT study (ASCO 2001). These studies used different chemotherapy regimens, but in the community, the better tolerated regimen of carbotaxol is becoming more and more common. This study supports the use of concurrent chemoradiation using these newer agents as well. Obviously, as more aggressive therapy is used, toxicity also increases, again which is consistent in this study, with a much higher incidence of esophagitis in the concurrent arms. What is against historical data is the poor results in the induction concurrent arm. This is especially distressing, as this is often what is done in the community. Explanations for this are multiple. Most likely, this study is simply underpowered so that skewed results are possible. In addition, although the groups were statistically balanced, there were more patients with weight loss and lower KPS in the induction/concurrent group. However, the other possibility is that, with the use of aggressive induction chemotherapy, the concurrent chemoradiation becomes more toxic and less tolerated. This is evident by only 46% of the patients in the induction/concurrent arm finishing all of their cycles of chemotherapy. Regardless, the use of concurrent chemotherapy is supported by this study, although its use should be reserved for those patients with little or no weight loss and an excellent KPS.

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