Overall Survival with Cisplatin and 5-Fluorouracil Neoadjuvant Treatment in Patients with Esophageal Cancer: Single-Center Experience

Abstract

Background: The survival benefit of neoadjuvant chemotherapy in patients undergoing surgery for esophageal cancer is unclear. Patients and Methods: We retrospectively identified 37 patients with resectable esophageal squamous cell carcinoma or adenocarcinoma, who prior to surgery received 2 cycles of chemotherapy, consisting of cisplatin 80 mg/m² as 3-h intravenous infusion on day 1 followed by 5-fluorouracil 1,000 mg/m² as 96-h continuous infusion on days 1–4, separated by a 3-week interval. Surgery was performed 3–5 weeks after the start of the second cycle of chemotherapy. Results: The overall response rate was 30% (all partial responses). All patients underwent surgery, 32 with esophagectomy (29 transhiatal, 3 transthoracic). Median overall survival (OS) in all patients was 23 months, and was longer in responding than in non-responding patients (32 vs. 19 months). 5 patients with locally unresected tumor and 18 patients with microscopic surgical margin involvement (R1) underwent postoperative chemoradiotherapy or radiotherapy. Median OS in patients after radical tumor resection (R0) was comparable with that in patients who underwent R1 resection (25 vs. 23 months). Conclusions: This retrospective analysis suggests that neoadjuvant chemotherapy prolongs survival in patients with esophageal cancer who responded to chemotherapy compared with non-responding patients.

Prospective Phase II Study of Neoadjuvant Therapy with Cisplatin, 5-Fluorouracil, and Bevacizumab for Locally Advanced Resectable Esophageal Cancer

“…However, compared with a group of historicalcontrolstreatedwithcisplatinand5-FUalone [13], the addition of bevacizumab did not improve the resection rate,PFS,OS,or1-and3-yearsurvivalrates. The biologic effects of neoadjuvant treatment appear to specificallyinfluencetheextentofsurgery,anditissuggested that it is this influence which confers the survival advantage [1,18].Inourstudy,theincidenceofunresectabletumorswas greater than in the group of historical controls (25 vs. 13%, p = 0.05), and the addition of bevacizumab to neoadjuvant chemotherapy did not increase the R0 resection rate (43 vs. 44%).MedianOSwassimilarinrespondersvs.non-responders(16vs.15months)whereasinthehistoricalcontrolsitwas longerinpatientswhorespondedtochemotherapycompared with non-responders (32 vs. 19 months).…”

“…Interestingly, the onlysignificantdifferencewasinmedianOSinpatientswho responded to neoadjuvant therapy, which was 16 months inthephaseIIstudyvs.32monthsinthehistoricalcontrols (p=0.05). Theapparentlackofeffectofbevacizumabontherateof distant metastases is counterintuitive if neoadjuvant therapy with bevacizumab is expected to reduce micrometastases presentatthetimeofdiagnosis.Theadditionofbevacizumab tochemotherapyinpatientswithadvancedgastroesophageal cancerhasdemonstratedpromisingactivityinphaseIIstudies,withresponseratesof42-67% [10][11][12].Inourstudy,the responseratewas39%whichwassimilartothatwithcisplatin and5-FUalone(30%) [13].Similarly,theadditionofbevacizumabdidnotleadtoanincreaseintheR0rate.Itispossible thatthesimilarresponseratewasresponsibleforthesimilar R0resectionrate.…”

“…Survival time wasmeasuredfromthedateofdiagnosistodeathorwascensoredatthe time that the patient was last known to be alive. Median survival times wereestimatedusingtheKaplan-Meiermethod.PFSwasdefinedasthe timefromsurgerytodiseaserelapse.Inaddition,theresultswerecomparedwithahistoricalcontrolgroupof37patientswhoreceivedthesame regimenofneoadjuvantcisplatinand5-FUalone [13].…”

“…Idelevich/Kashtan/Klein/Buevich/BenBaruch/ Dinerman/Tokar/Kundel/Brenner historical controls [13]. Of these patients, none achieved a CR,11(30%)achievedaPR(ORR30%),21(57%)hadSD, and5(13%)hadPD.Ofthe14patientswithsquamouscell carcinoma,5(34%)hadaPR,7(60%)hadSD,and2(6%) had PD.…”

“…TheaimofthisprospectivephaseIIstudywastoinvestigate the efficacy and tolerability of neoadjuvant chemotherapywithcisplatinand5-FUplusbevacizumabforpatients with locally advanced resectable esophageal cancer (LAREC).Inaddition,wecomparedtheresultsofthisstudy with those of a previous group of 37 patients at our center, whoreceivedneoadjuvantchemotherapywiththesameregimenofcisplatinand5-FUalone [13]. Cisplatin+5-FU+BevacizumabNeoadjuvant TherapyinEsophagealCancer 429 disease(PD).Ofthe6patientswithsquamouscellcarcinoma, 2 (33%) had a PR, 2 (33%) had SD, and 2 (33%) had PD.…”