“CONCURRENT CHEMORADIATION (CChRT) FOR STAGE III NON-SMALL CELL LUNG CANCER (NSCLC):
A PHASE II STUDY FROM GALICIAN LUNG CANCER GROUP”
J. Casal1, C. Ponte2, C. Senín1, B. Campos3, XL. Firvida4, M. Carmona5, E. Hernández6, MD. López7, I. Formoso2, M. Lázaro1, S. Vázquez3, MC. Areses4, C. Rodríguez5, C. Pena8, MJ. Villanueva1
1Sº Oncoloxía
Medica (OM) Complexo Hospitalario Universitario (C. H. U.) de Vigo, Spain; 2Sº Oncoloxia Radioterápica (OR) C.H. U. de Santiago, Spain; 3Sº OM H. U. Lucus Augusti de Lugo, Spain; 4Sº OM. C.H. U. de Ourense, Spain;
5Sº OM C.H. U. de Santiago, Spain; 6Sº OR C.H.U. de Vigo, Spain; 7Sº OR C.H.U. de Ourense, Spain; 8Sº OM C.H. de Pontevedra, Spain.
ABSTRACT TEXT
I I I .- R E S U L T S:
Background: Combined cytotoxic chemotherapy and radiation therapy is established as the standard treatment for patients with medically inoperable or
technically unresectable stage III NSCLC. Multiple randomized studies and meta-analyses demonstrate that CChRT results in improved survival compared
with sequential chemo-radiotherapy or radiotherapy alone. The aim of our study was to evaluate the effectiveness and toxicities of CChRT with biweekly Docetaxel (D) and Cisplatin (C) and thoracic radiotherapy, after one cycle D-C induction chemotherapy.
Methods: Between May 2009 and November 2012, 53 chemo-naive p with histologically confirmed inoperable locally advanced NSCLC, stage IIIAN2/IIIB
(no pleural T4), PS 0-1 and adequate lung function (FEV1 > 1.1, V20 < 25%) were included: one cycle of D 75 mg/m2 on day 1 and C 40 mg/m2 days 1-2
followed at 21 days by CChRT with bi-weekly D 40 mg/m2 and C 40 mg/m2 for four courses, during conformal thoracic radiotherapy (66 Gys, 180
cGy/day). The primary objective was overall survival (OS); secondary objectives were progression free survival (PFS), response rate (RR) and toxicity.
Median follow-up: 17,8 months.
Results: The p characteristics were: mean age 59,4 years (34-75); male/female 47/6; ECOG PS 0/1 in 17/36 p; squamous/adeno/large cell carcinoma:
53%/34%/13%; stage IIIAN2 15 p (28.3%) and stage IIIB 38 p (71.7%). All p were evaluable for response and toxicity. RR: 6 CR, 37 PR (RR 81.8%; 95%
CI:71-92), 4 SD (7.6%) and 6 PD (11.3%). The median PFS was 14 months (95% CI:11-17) and median OS was 21 months (95% CI:9-32). The PFS at 1/2
years were 55%/32% and the OS at 1/3 years were 82%/50%. A total of 53 cycles of D-C induction chemotherapy were given; main toxicities (NCI-CTC
3.0) per p Grade (g) 1-2/3-4 (%) were as follows: neutropenia 1.8/15; anemia 11.3/0; nausea/vomiting 26.4/1.8; diarrhea 22.6/3.7; fatigue 35.8/0; there
were three episodes of hospitalization: febrile neutropenia 2 p and g3 diarrhea 1p. Main toxicities per p in CChRT (D-C doses: 203, 3.8 per p; mean
doses RT: 64,6 Gys) were g1-2/3 (%): neutropenia 28.3/5.6; anemia 62.2/0; esophagitis 50.9/3.7 and pneumonitis 32/0; nausea/vomiting 20.7/0; fatigue
37.7/3.7; there were four episodes of hospitalization: febrile neutropenia, 2 p and g3 esophagitis, 2 p.
Conclusion: CChRT with bi-weekly Docetaxel and Cisplatin and thoracic radiotherapy is a feasible treatment option for inoperable locally advanced stage
III NSCLC, showing good clinical efficacy and tolerability with acceptable long-term survival.
I I I . C .- E F F I C A C Y (%) :
I I I . A .- Patients Characteristics (n = 53)
Median age (range), years
59,4 (34 – 75)
Sex
Male
Female
47 (88 %)
6 (12 %)
ECOG (Performance Status)
0
1
17 (31,4 %)
36 (68.6 %)
Histology
I .- B A C K G R O U N D:
Squamous
Adenocarcinoma
Large cell
28 (52.8 %)
18 (33.9 %)
7 (13.3 %)
T1-3 N2
15 (28.3 %)
T4 N0-2
T1-3 N3
T4 N3
27 (50.9 %)
7 (13.3 %)
4 (7.5 %)
RESPONSE
P
%
CR
6
11.3
PR
37
69.8
OR
43
81.8
SD
4
7.6
PD
6
11.3
95% CI
SURVIVAL
71 - 92
MEDIAN
(months)
95% CI
1 year
%
2 years
%
3 Years
%
OS
21
9 - 32
81.8
49.7
30.2
SLPR
14
11 - 17
55.1
31,8
n.a.
I I I . D .- T H E S U R V I V A L C U R V E S (KAPLAN-MEIER):
Stage III A
 Combined cytotoxic chemotherapy and radiation therapy is established as the standard treatment for patients with medically inoperable or
technically unresectable stage III NSCLC.
Stage III B
 Multiple randomized studies and meta-analyses demonstrate that CChRT results in improved survival compared with sequential chemo-radiotherapy
or radiotherapy alone. A clearly superior regimen has not identified.
 Docetaxel (D) has been shown to posess good single activity against NSCLC as well as radiosensiziting properties both alone and sinergistically with
Cisplatin (C).
Weight loss < 5%
 The aim of our study was to evaluate the effectiveness and toxicities of CChRT with bi-weekly Docetaxel (D) and Cisplatin (C) and thoracic
radiotherapy, after one cycle D-C induction chemotherapy.
6 (11.3 %)
Evaluable
Response
Toxicity
I I . A .- M A T E R I A L A N D M E T H O D S:
 SELECTIVE CRITERIA: - Age < 75 years.
 PRIMARY OBJECTIVE:
- Histological confirmation.
53 (100 %)
53 (100 %)
Overall survival (Kaplan-Meier)
- Stage: IIIA – IIIB (except pleural effusion T4) (AJCC’97).
I I I . B .- T O X I C I T Y (per p)
 SECONDARY:
- Evaluable or measurable disease.
Progresion free survival, (Kaplan-Meier).
- PS 0-1 (WHO grade).
Response rate (Recist).
- Normal organic functions;
a) INDUCTION D-C: 53 cycles (1 per p)
b) CChRT: 50 p: D-C doses: 203 (3.8 per p)
mean RT doses: 64,6 Gy (41-66.6)
Toxicity (CTC-NCI v3.0 and RTOG.
- FEV1 > 1.1 litres. V20 < 25%.
- Weight loss < 5 %.
TOXICITIES
g 1-2
g 3-4
TOXICITIES
g 1-2
g3
- No previous treatment or serious underlyne disease.
 50 patients (p) with locally advanced NSCLC were included from June/2009 to July/2012.
neutropenia
1.8
15
neutropenia
28.5
5.6
 MEDIAN FOLLOW-UP: 17,8 Months.
anemia
11.3
0
anemia
62.2
0
n/vomiting
26.4
1.8
esophagitis
50.9
3.7
diarrhea
22.6
3.7
pneumonitis
32
0
fatigue
35.8
0
n/vomiting
20.7
0
stomatitis
12.9
0
fatigue
37.7
3.7
I I . B .- T R E A T M E N T P L A N:
Induction
chemotherapy
DOCETAXEL 75 mg/m2
CChRT
40 mg/m2
THORACIC RT
(66 Gys: 180 cGy/d)
CISPLATIN
Days
40 mg/m2
12
22
36
50
www.cancerpulmongalicia.org
64
E
V
A
L
U
A
T
I
O
N
92
follow - up
2 hospitalisations:
febrile neutropenia: 1 p
g3 diarrhea: 1 p
4 hospitalizations:
febrile neutropenia: 2 p
g3 Esophagitis: 2 p
C O N C L U S I O N S:
 CONCURRENT CHEMORADIATION WITH BI-WEEKLY DOCETAXEL AND CISPLATIN AND THORACIC RADIOTHERAPY, AFTER
ONE CYCLE OF INDUCTION CHEMOTHERAPY WITH D-C, IS A FEASIBLE TREATMENT OPTION FOR IRRESECABLE
LOCALLY ADVANCED STAGE III A – III B NON SMALL CELL LUNG CANCER.
 AN GOOD CLINICAL ACTIVITY, TOLERABILITY AND MEDIAN OVERALL SURVIVAL WERE OBSERVED.
 AN ACCEPTABLE LONG TERM SURVIVAL WAS ACHIEVED.
IASLC, 15TH WCLC 2013; Sydney: # 1010