Seasoning with... CPPD, 5FU? Uhm... Chopped Chopped first or at the end? BBQed, Steamed or microwaved Then... cooked or..... Marinating? With Taxanes, oxaliplatin Yummmy Sterilising? With heat and chemicals Oesophagus Think this is hard... Wait till you see the rest The Surgical/ Medical/ Rad Onc dilemma

OESOPHAGEAL CARCINOMA Uncommon cancer, accounting for approximately 1% of all malignancies and 6% of all gastrointestinal malignancies. Significant advances have been made in the staging and clinical treatment of patients with oesophageal cancer, the outcome for these patients remains bleak.

CARCINOMA OF THE OESOPHAGUS New cases per year Deaths per year 5 y OS Worldwide412,000338,000NR United States13,90013, % Europe44,00040,00012% Australia %

SURGERY ALONE

The more we chop,..... the better it gets! Dr Lee Surgeon

Surgical 5-year survival Stage I 50-80% Stage IIA 30-40% Stage IIB 10-30% Stage III 10-15%

RADIATION THERAPY ALONE COMPARED WITH CHEMORADIATION

A bit well done Dr Cook

NEJM, Volume 326: June 11, 1992Number 24 Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus A Herskovic, K Martz, M al-Sarraf, L Leichman, J Brindle, V Vaitkevicius, J Cooper, R Byhardt, L Davis, and B EmamiJune 11, 1992 CRTXRT median survival months y Survival y Survival3810 survivors257 G3-4 SE Local recurrence 16%24% 121 pts with SCC or adenocarcinoma of the thoracic oesophagus N- 61 CIV 5FU 1000 d 1-4 and cisplatin 75 d1 plus 50 Gy of XRT N=60 64 Gy of XRT alone The trial was stopped after the accumulated results in 121 patients demonstrated a significant advantage for survival in the patients who received CRT RTOG 8501

TI-3N0-IMO lesions adeno or SCC RT arm: 64 Gy (10 Gy per week in five fractions) CT-RT arm, RT 50 Gy plus Cisplatin 75 day 1, and 5FU days 1-4 W 1 and 4 Cisplatin 75 day 1, and 5FU days 1- 4 q 3/52 x 2

Time to first failureOverall Survival RTOG 8501 at 5 years, survival rates were 30% and 0%,

Oesophageal carcinoma: Single agent response rate Older drugsNewer drugs DrugResponse rate %DrugResponse rate % Antimetabolites 5 FU MTX Gemcitabine Xeloda Pemetrexed S Antibiotics Mitomycin30 Anthracyclin Doxorubicin Epirubicin Heavy Metal Cisplatin Carboplatin 23 9 OxaliplatinNA Topoisomerase Inh. Etoposide8Irinotecan21 Taxanes Paclitaxel Docetaxel 13 21

NEOADJUVANT CHEMORADIATION COMPARED WITH SURGERY ALONE Dinner is ready,.. I hope so anyway

113 patients with adenocarcinoma of oesophagus Surgery N= 55 Cisplatin 75 d7 and 5FU 15 mg/kg/d CIV d1-5 W# 1 and 6 concurrent with Radiotherapy 40 Gy in 3 weeks N=58 surgery IRISH TRIAL

Median survival was 16 vs 11 months p= 0.01

100 patients, squamous and adenocarcinoma Transhiatal oesophagectomy Cisplatin 20mg/m2/d d1-5 and d FU CIV 300mg/m2/d d1- 21 Vinblastin 1mg/m2/d d 1- 4 and Plus Radiation 45 Gy 1.5 Gy bd Transhiatal oesophagectomy

3 year survival 30% vs 16% p=0.15 mS= 17 months Median survival 50 mo vs 12 mo

282 patients with SCC of oesophagus Surgery N= 55 Cisplatin 80 d1 and 21 concurrent with Radiotherapy 37 Gy 3.7 Gy fr split –course with 2 week interval surgery EORTC

m survival = 18.6 mo

Cisplatin 80 day 1, fluorouracil 800 days 1–4, with concurrent radiotherapy of 35 Gy given in 15 fr TROG IG 9401

M survival 19 vs 22 mo HR 0.89 p=0.57 Neoadjuvant therapy had a 13% pathologic complete resection. Also were more likely to undergo curative resection and have negative lymph nodes on histologic examination.

56 patients with SCC and adeno of oesophagus Surgery Cisplatin 100 d1, 29 and 5FU 1000 CIV d1-4, concurrent with Radiotherapy 50.4 Gy Surgery 5 yS 39 vs 16%, p=0.008

THANKS AND HAVE A GOOD NIGHT THANKS AND ENJOY YOUR LUNCH