CONCURRENT CHEMORADIATION FOR

CERVICAL CANCER
 Neoadjuvant chemotherapy trials showed no benefit over RT alone.
• Tattersall (JCO, 1995)
– EC3 (epirubicin, cisplatin)
– Inferior local control and OS
• Kumar (Gynecol Oncol, 1994)
– BIP2 (bleomycin, ifosfamide-mesna, cisplatin)
– Similar OS and DFS, toxic: 2 CT related deaths
• Souhami (JCO, 1991)
– BOMP3 (bleomycin, vincristine, mitomycin, cisplatin)
– Inferior OS, toxic
 Five trials provided evidence for concurrent cisplatin-based chemotherapy.
CONCURRENT CISPLATIN-BASED CHEMOTHERAPY VERSUS RT ALONE
SURVIVAL (%)
POPULATION CHEMO RT CCRT p VALUE TOX
Keys IB2 (pre-op) C 40 q1w 68 84 0.008
GOG 123 x6c
Peters pIA2-IIA + any: CF 70/5g 63 81 0.010
SWOG PLN+, R1, q3w x4c
8797 microscopic
parametrial
involvement
(post-op)
Eifel IIB-IVA, IB-IIA CF 75/5g 41* 67 0.004 Similar rates of
RTOG 9001 >5cm, PLN+ q3w x3c late
complications
 Five trials provided evidence for concurrent cisplatin-based chemotherapy.
CONCURRENT CISPLATIN-BASED CHEMO VERUS HYDROXYUREA
CHEMO SURVIVAL (%)
POP H C H C p VALUE TOX
Whitney IIB-IVA H 80/k CF 50/4g 39.8 50.8 0.018
GOG 85 2/w q3w x2
Rose IIB-IVA H 3g 2/w C 40 q1w 39 64 0.002 Hematoxicity
GOG 120 x6c increased with
H 3g 2/w CF 50/4g 39 66 0.002 CHF than either
+ H 2g C or H.
2/w
 POPULATION AND TREATMENT ARMS

• IIB-IVA, PALN-negative per

radiological investigation
• Group 1. CF 100/5g over 5d q4w
x 3c
• Group 2. C 30 q1w x 6c
 CONCURRENT CISPLATIN-BASED CHEMOTHERAPY
WEEKLY CISPLATIN
Keys (GOG 123) IB2 (pre-op) C 40 q1w x6c C 240
Rose (GOG 120) IIB-IVA C 40 q1w x6c C 240
Kim, 2005 IIB-IVA C 30 q1w x 6c C 180
3-4 WEEKLY CF
Peters (SWOG 8797) pIA2-IIA + any: PLN+, R1, CF 70/5g q3w x4c CF 280/20g
microscopic parametrial
involvement (post-op)
Eifel (RTOG 9001) IIB-IVA, IB-IIA >5cm, PLN+ CF 75/5g q3w x3c CF 225/15g
Whitney (GOG 85) IIB-IVA CF 50/4g q3w x2c CF 100/8g
Kim, 2005 IIB-IVA CF 100/5g q4w x3c CF 300/15g
 EXTERNAL BEAM RADIOTHERAPY
• 41.4/23 (IIB); 50.4/28 (IIIA-IVA)
• Box technique without midline shielding, 15MV photons
• Target volumes
– whole uterus, primary mass, paracervical, parametrial and uterosacral regions, external
iliac, hypogastric and obturator lymph nodes
• AP/PA
– 1.5-2cm lateral to the widest bony margin of the true pelvis
– Superior border: mid-L5
– Inferior border: 2cm below lowest extension of primary tumor or lower portion of
obturator foramen
• Lateral
– Anterior border: anterior 1/3 of symphysis pubis
– Posterior border: S2-S3 interface based on the extent of the primary tumor
 Ir-192 INTRACAVITARY HDR-BT

• Done after completion of EBRT

• 35/7 (IIB), 30/6 (IIIA-IVA) to pt A, MWF
• Parametrial boost to 60-65/CF per EBRT, TTh
• Intracavitary HDR-BT and a parametrial boost were not delivered on the
same day
 STUDY ENDPOINTS

• Compliance
• Acute toxicity (RTOG criteria)
• Response (CR, PR, clinical or radiologic – MRI 3mos post)
• Failure (LR, DM)
• Survival (DFS, OS)
 For the definitive CRT trials, compliance rates of 70-80% were achieved.*
CONCURRENT CISPLATIN-BASED CHEMOTHERAPY
WEEKLY CISPLATIN
Keys (GOG 123) IB2 (pre-op) C 40 q1w x6c C 240
Rose (GOG 120)* IIB-IVA C 40 q1w x6c C 240
Kim, 2005 IIB-IVA C 30 q1w x 6c C 180
3-4 WEEKLY CF
Peters (SWOG 8797) pIA2-IIA + any: PLN+, R1, CF 70/5g q3w x4c CF 280/20g
microscopic parametrial
involvement (post-op)
Eifel (RTOG 9001)* IIB-IVA, IB-IIA >5cm, PLN+ CF 75/5g q3w x3c CF 225/15g
Whitney (GOG 85)* IIB-IVA CF 50/4g q3w x2c CF 100/8g
Kim, 2005 IIB-IVA CF 100/5g q4w x3c CF 300/15g
RESULTS
PATIENT CHARACTERISTICS
COMPLIANCE
TOXICITY
FAILURE AND SURVIVAL RATES
 UPDATED RESULTS (2008)

• n=155
• Median follow-up: 39mos
• Compliance: 60% vs 71%, in favor of weekly cisplatin
• Acute grade 3/4 hematologic toxicity: 43% vs 26% (p = 0.037)
• CR: 91% vs 91%
• 4y OS and PFS: 70% and 67% vs 67% and 66%