A prospective study comparing induction chemotherapy followed by chemoradiation versus chemoradiation alone in stage III NSCLC.

Dr. Rajib Bhattacharjee, PGT, IPGME&R, KolkataDr. Subir Pal, PGT, IPGME&R, KolkataDr. Somnath Roy, SR, IPGME&R, KolkataDr. Siddhartha Basu, Professor & HOD, IPGME&R, Kolkata

Introduction

Lung cancer is the major cause of cancer related deaths worldwide.

About 85% of lung cancers are of non small cell histology.

In our OPD we most commonly encounter stage III NSCLC (locally advanced).

Locally advanced disease warrants curative approach in the form of surgery or radiotherapy

Treatment options for stage III disease

•Operable •Stage III ASurgery•Stage III B•Inoperable stage III A

Conc. CT-RT

•Stage III B•Inoperable stage III A

Induction chemo f/b RT

Sequential CT-RT v RT alone

Induction chemo with Cisplatin & Vinorelbin f/b RT(60Gy) was compared to RT alone

CT-RT RT alone Tumor response

56% 43%

Median survival

13.7 mo

9.6 mo

CONCLUSION – Sequential CT-RT improved tumor response and median survival BUT80-85% patients still die within 5 years due to loco-regional and distant failure in both the arms.

Conc. CT/RT v sequential CT f/b RT

CONCLUSION – Concurrent chemoradiation showed survival benefit over sequential therapy.

Can we mix the two treatments ??

The Jury is still out !!!

Aims and objectives

• To compare efficacy of adding induction chemotherapy to chemoradiation with chemoradiation alone.

• PRIMARY END POINT1. Response evaluation as per RECIST guidelines.2. Comparison of acute toxicities according to RTOG/EORTC

radiation morbidity criteria.

• SECCONDARY END POINT1. Disease Free Survival (DFS).2. Progression Free Survival (PFS).

Study schema

Assessed for

eligibility

n = 56

Randomized

n = 53

Excluded

n = 3

Allocated to intervention in

arm An = 27

Did not receive intervention

(n=1)

Allocated to intervention in

arm Bn = 24

Did not receive intervention

(n=1)

Allocation

Lost to follow up

n = 2

Lost to follow up

n = 1

Analyzedn = 25

Analyzedn = 23

Follow up

Analysis

Concurrent CT-RT with Paclitaxel(50mg/m2) iv weeklyCarboplatin(AUC2) iv weeklyRT dose – 66 Gy in 2 Gy/# Arm A

n = 25

Induction CT withPaclitaxel(200mg/m2) iv 3weeklyCarboplatin(AUC6) iv 3weekly2 cyclesConcurrent CT-RT As Arm A Arm B

n = 23

Baseline characteristics and median fallow upBaseline characteristics Age & sex distribution, performance status, T & N stages

and histology were similar in the two arms (p>0.05). Sex distribution – male in Arm A – 88% Arm B – 95.65% [p =

0.61] Smoker – in Arm A – 84% Arm B – 86.95% [p = 1.00]

Median follow up Arm A – 8 months (2 – 14months) Arm B – 8 months (2-16 months).

Response evaluation

Arm

Response

Total CR PR SD PD

A 5 20%

9 36%

5 20%

6 24%

25100%

B 628.06%

1043.47%

417.39%

313.04%

23100%

Total

1122.91%

1939.58%

918.74%

918.74%

48100%

Arm A Arm B05

101520253035404550

Chart Title

CR PR SD PDP = 0.76

Recurrence after complete response

Arm

Recurrence after CR

Total No Yes

A

3 60%

2 40%

5 100%

B 5 83.33%

1 16.67%

6 100%

Total

8 72.72%

3 27.27%

11 100%

Arm A Arm B01234567

CR Disease freeRecurrenceP = 0.54

Disease Free Survival

Progression Free Survival

Acute toxicity comparison Hematotoxicity

Arm Toxicity grade Total

0 1 2 3

A 10 40%

9 36%

5 20%

1 4%

25 100%

B 1252.17%

939.13%

28.69%

0 0%

23 100%

Total 2245.83%

1837.49%

714.58%

1 2.08%

48 100% Arm A Arm B0

2468

101214

Grade 0 Grade 1Grade 2 Grade 3P = 0.25

Acute toxicity comparison Pulmonary toxicity

Arm

Toxicity grade

Total 0 1 2 3

A 11 44%

9 36%

4 16%

1 4%

25 100%

B 730.43%

1252.17%

417.39%

0 0%

23 100%

Total 1837.49%

2143.74%

816.67%

12.08%

48 100%

Arm A Arm B02468

101214

Grade 0 Grade 1Grade 2 Grade 3

P = 1.00

Acute toxicity comparison Aerodigestive tract toxicity

Arm

Toxicity grade

Total 0 1 2 3

A 9 36%

12 48%

3 12%

1 4%

25100%

B 417.39%

1252.17%

521.73%

28.69%

23100%

Total

1327.08%

24 50%

816.67%

36.25%

48100%

Arm A Arm B02468

101214

Grade 0 Grade 1Grade 2 Grade 3P =

0.31

Acute toxicity comparison Skin toxicity

Arm

Toxicity grade

Total 0 1 2

A 19 76%

5 20%

1 4%

25 100%

B 19 82.6%

4 17.39%

0 0%

23 100%

Total 38 79.16%

9 18.74%

1 2.08%

48 100%

Arm A Arm B02468

101214161820

Grade 0 Grade 1Grade 2P = 0.73

Summary • In our study, 48 patients were finally

analyzed in two arms. Patients in both arms had similar baseline characteristics.

• Majority of the patients were male smokers.• The overall response rate with induction

chemotherapy was higher but it did not attain statistical significance.

• The acute toxicities were similar in both arms.• DFS & PFS for both the arms were similar.

Conclusion

In terms of treatment response, survival and acute toxicity profiles, there was no significant difference between induction chemotherapy followed by chemoradiotherapy and sole chemoradiotherapy in our study.

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