Neoadjuvant chemotherapy and hyperfractionated radiotherapy with concurrent low-dose chemotherapy for squamous cell esophageal carcinoma.
OBJECTIVE
We conducted a prospective study of neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction.


METHODS
Thirty-two patients, 30 men, 2 women, mean age 56.2+/-8.9 years, with resectable squamous cell carcinoma of the esophagus (TNM stage I=4, IIA=4, IIB=13, III=11) were included. Chemotherapy, CDDP (80 mg/m2 D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and l-folinic acid (200 mg/m2, D1-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy.


RESULTS
No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelets, mucositis) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n=18), persistent microscopic residues (n=4), or not significant modification (n=4). Survival at 1, 2, and 3 years was 81, 61, and 51.6% and disease-free survival was 75, 59, and 54% respectively.


CONCLUSIONS
This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 3-year survival reached 52%, a very high rate in our experience.
Raoul
J L
JL
Centre Régional de Lutte Contre le Cancer, Eugène Marquis, Centre Hospitalier Universitaire de Rennes, France.
Le Prisé
E
E
Meunier
B
B
Heresbach
D
D
Campion
J P
JP
Launois
B
B
D000931:Antidotes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D016896:Treatment Outcome
D000931:Antidotes; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil