Preoperative fluorouracil (FU)-based chemoradiation +/-

weekly oxaliplatin in locally advanced rectal cancer.

Pathologic response analysis of the STAR (Studio Terapia

Adiuvante Retto)-01 randomized phase III trial.

C. Aschele, C. Pinto, S. Cordio, G. Rosati, A. Tagliagambe,

S. Artale, P. Rosetti, S. Lonardi, L. Boni, L. Cionini, on behalf of STAR Network Investigators.

BACKGROUND AND RATIONALE

Locally-advanced rectal cancer

high rates of distant metastases (30 - 35 %)

+ve CRM in 10-30 % of “resectable” tumors

Oxaliplatin

improves the efficacy of FU-based CT (colon ca.)

radiosensitizing properties (exp. models) promising activity with pre-op RT and FU

(phase I-II studies)

STUDY OUTLINE

R

RT 50.4 GyFU 225 mg/m2/day PVI OXA 60 mg/m2 weekly x 6

RT 50.4 GyFU 225 mg/m2/day PVI

TME

FU/LV(bolus or CI, center choice)

6-8wks

• stage• center

MAIN INCLUSION CRITERIA

adenocarcinoma within 12 cm from anal verge cT3-T4 and/or cN+ resectable (no infiltration of

the pelvic wall, prostate, bladder base)

cM0

STUDY END-POINTS

primary: overall survival- 30% RR in mortality rates (3-y S: 75 --> 82%)- 80% power - alpha error: 0.05

secondaries:• pathologic complete response (pCR):- all path reports available (cut-off data 01/03/09)- 12% --> 25%; 90% power

• disease-free survival • safety

STUDY POPULATION

747: randomizedresponse/survival analyses

379FU/RT

368FU/OXA/RT

379 353

5 never started- consent withdrawal (2)- squamous histology (1)- immediate surgery (2)

10 never started (3) consent withdrawal(2) squamous /melanoma(1) immediate surgery(2) only RT(2) different chemo

5 received FU alone

732: treatedsafety/compliance analyses

PATIENTS CHARACTERISTICS

FU/RT FU/OXA/RT

(n=379)(n=368)

Age, yearsmedian 63 62

Sex, %males 68 67 females 32 33

ECOG PS, %0 87 88 1-2 13 12

FU/RT FU/OXA/RT(n=379) (n=368)

T stage, %T1-2 2 5 T3 78 78 T4 20 17

N +, % 64 67

cm from anal verge

median 6 6TRUS: 33; pelvic CT scan: 261; both 453

TUMORS CHARACTERISTICS

TREATMENT COMPLIANCE:OXALIPLATIN

weekly courses patients, n*

1 3 2 6

3 26 4 24 5 60

83% > 6 233 66%

* missing data=1

mean actually delivered dose intensity:58.3 mg/mq/wk

patients, % FU/RT FU/OXA/RT

(n=379) (n=353)FU > 5 weekly courses 95 88

RT full dose +/- 10 % 97 90

TREATMENT COMPLIANCE:5-FU and RT

TOXICITY % of patients

FU/RT FU/OXA/RT (n=379) (n=353)

pgrade III-IV any type 8 24<.0001 diarrhea 4 15<.0001 radiation dermatitis 2 5

0.038grade II-IIIneurosensory 0.5/0 36/1<.0001

Tx related deaths 0.3 (1) 0.6 (2)

patients, % FU/RT

FU/OXA/RT (n= 379) (n= 368)Operated 9696 LAR 72 73 APR 19 18 other 4 5

Median interval 52 days 53 days

Deaths < 60 d 0.8 (3) 0.8 (3)

SURGERY

patients, % FU/RT FU/OXA/RT

(n= 379) (n= 368) p

ypT0N0 16 16 0.94(95% cl) (13-20) (13-20)

pathologic CR

patients, % FU/RT

FU/OXA/RT (n= 379) (n= 368)

pT0 17 18pT1-2 35 35 pT3-4 44 42

diameter, mm median (range) 26 (1-100) 24 (2-80)

CRM+ 6 4*

PATHOLOGY (T)

* p=0.13

patients, % FU/RT

FU/OXA/RT (n= 379) (n= 368)examined median 12 11 range 0-47 0-42

pN0 70 68

pN1 17 17 pN2 8 10

PATHOLOGY (N)

patients, n FU/RT FU/OXA/RT (n=379) (n=368) p

pM1 11 (3%) 2 (0.5%) 0.014 liver 6 1 peritoneal 4 1 nodes 1 -

cM1 5 - liver 4 - liver+lung 1 -

Overall 16 2

M+ at SURGERY (unplanned / exploratory)

SUMMARY

The addition of OXA to FU-based preop CRT:

- does not improve local tumor response

- significantly increases toxicity (still manageable) and slightly reduces treatment compliance (but surgery OK)

- is associated with a lower frequency of occult distant metastases at surgery

CONCLUSIONS

These data do not support the addition of OXA to pre-op FU/RT to maximize tumor shrinkage in LARC (radiosensitizing properties unconfirmed)

OXA-based regimens may not be the optimal back-bone for incorporation of new radiosentizing agents

The observation of a lower number of distant mts at surgery lends support to the study primary hypothesis (confirmation with more mature data is required)

Follow-up is ongoing to assess the impact on efficacy end-points. Stay tuned!

StudioTerapia

Adiuvante

Retto

ALBA

AREZZO

AVIANO

BERGAMO

BOLOGNA RAVENNA

BOLZANO RIMINI

CAMPOSAMPIERO RIONERO VULTURE

CASTELLANZA LUGO ROMA

CATANIA MANTOVA SANREMO

CATANZARO MASSA CARRARA SARONNO

CATTOLICA MILANO HUMANITAS SAVONA

CUNEO MILANO NIGUARDA SONDRIO

FAENZA MILANO SAN PAOLO TARANTO

FANO MODENA THIENE

FELTRE MONZA TORINO

FORLI' NOVARA TRENTO

GENOVA PADOVA UDINE

LEGNAGO PISA VENEZIA

LIVORNO POTENZA VIGEVANO

THANKS TO ALL THE PATIENTS,

INVESTIGATORS and DATA-MANAGEMENT

STAFF!