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Esophagous

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Concurrent Chemoradiation
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Treatment Recommendations Based on Stage

Neoadjuvant Chemoradiotherapy
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50 Gy in 25 fractions over 5 weeks,
CISPLATIN IV on the first day of weeks 1, 5, 8, and 11
FLUOURACIL, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11


REF: JAMA; 281(17):1623-7 1999 N = 134: squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a Karnofsky score of at least 50.

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Chemoradiotherapy
Walsh Protocol

5FU 15 mg/kg/day IV over 16 hours DAYS 1-5
After 1 day of hydration with 2 liters NS,
Cisplatin 75 mg/m2 IV over 8 hrs on day 7.
This cycle was repeated in week 6.
XRT was begun on the 1st day of the first course of
chemotherapy & given for a total of 15 days (days 1 to 5,8 to 12,& 15 to 19).

REF=NEJM 335:462, 1996
N= 113 . At the time of surgery,23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases,as compared with 45 of the 55 patients (82%) who underwent surgery alone (P 0.001).13 of 52 pts (25%) who underwent surgery after multimodal therapy had pathologic CR. Median survival (multimodal therapy) = 16 months, vs 11 months for surgery alone (P 0.01). At 1, 2, & 3 years 52,37,& 32% of patients assigned to multimodal therapy were alive,as compared with 44,26,& 6% assigned to surgery,with the survival advantage favoring multimodal therapy reaching significance at 3 years (P 0.01).

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Atsushi

5FU 400 mg/m2 over 24 hours on days 1 to 5 and 8 to 12,
Cisplatin 40 mg/m2 IV over 2 hrs on days 1 & 8, & concurrent XRT (30 Gy in 15 fractions) over 3 weeks. GCSF was prophylactically administered to 35 patients. This schedule was repeated twice Q5 weeks, for a total radiation dose of 60 Gy, followed by 2 courses of 5FU (800 mg/m2 over 24 hours X 5 days) & cisplatin (80 mg/m2 on day 1).

REF= JCO 17:2915, 1999
N= 54 clinical T4 &/or M1 LN squamous cell
carcinoma of the esophagus.
Results: There were 21 patients with T4M0 disease,
one with T2M1 LYM, 17 with T3M1 LYM, & 15 with
T4M1 LN. 49 (91%) completed at least the chemoradiotherapy segment. The 18 patients (33%)
who achieved a CR included 9 (25%)
of the 36 with T4 disease and 9 (50%) of the 18 with
non-T4 disease. Major toxicities were leukocytopenia
& esophagitis; there were four (7%) treatment-related
deaths. Prophylactic filgrastim reduced the incidence
of grade 3 or worse leukopenia without improving
dose-intensity or response. With a median follow-up
duration of 43 months, median survival time was 9
months. The 3-year survival rate was 23%.

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Herskovic

4 Courses:
5FU 1000 mg/m2 QD X 4 days
Cisplatin (75 mg/m2 day 1) plus
5000cGy of radiation therapy
( 2courses with RT then 2 courses afterwards)


REF=NEJM 326:1593, 1992
The median survival = 8.9 months in the XRT group, vs
12.5 months in the patients treated with chemotherapy & radiation therapy. In the formergroup, the survival rates at 12 & 24 months were 33% & 10%, respectively, whereas they were 50% & 38% in the patients receiving combined therapy (P<0.001).

REF= JCO 15, 277, 1997.
Minimum follow-up time = 5 years for all pts. Median survival = 14.1 months & the 5-yr survival rate =27% in the combined treatment group, while the median survival= 9.3 months with no patients alive
at 5 years in the RT-alone group (P < .0001). Additional patients (69) were treated with the same combined
therapy and were analyzed. The results of the last group confirmed all of the results obtained with combined CT-RT in the randomized trial, with a median = 17.2 months & 3-yr survival rate = 30%.
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Other Chemotherapy Regimen:
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Cisplatin + Irinotecan

Cisplatin 30 mg/m2 IV over 30 minutes
Then
Irinotecan 65 mg/m2 IV over 30 minutes
Qweekly X 4 (=1 Cycle)
Repeat Cycle Q6weeks

REF= JCO 17:3270, 1999
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Cisplatin + Taxol

Taxol 200 mg/m2 IV over 24 hours DAY 1
Cisplatin 75 mg/m2 IV on DAY 2
GCSF start DAY 3
Repeat Q3 weeks

REF= Seminars in Oncology 24:S19 77-81, 1997
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Singel Agent Taxol (24 hr CI)
Taxol 250 mg/m2 IV over 24 hours
GCSF the day after
Repeat Q 3 weeks

REF= J Nat Cancer Inst 86:1086, 1994
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TREATMENT SUMMARY (REF=PDQ):
STAGE I
Standard: Surgery.

STAGE II
Standard:
1. Surgery.
2. Chemotherapy plus radiation therapy with or without subsequent surgery.

STAGE III
Standard:
1. Chemotherapy plus radiation therapy with or without subsequent surgery.
2. Surgical resection of T3 lesions.

STAGE IV
Standard:
1. Radiation therapy with or without intraluminal intubation and dilation.
2. Intraluminal brachytherapy can also provide palliation of dysphagia.
3. Nd:YAG endoluminal tumor destruction or electrocoagulation.
4. Chemotherapy has provided partial responses for patients with metastatic distal esophageal adenocarcinomas.

Link to PDQ web site