High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy

Pasini, Felice; Manzoni, Giovanni De; Pedrazzani, Corrado; Grandinetti, A.; Durante, E; Gabbani, Milena; Tomezzoli, Anna; Griso, C.; Guglielmi, Alfredo; Pelosi, Giuseppe; Maluta, S.; Cetto, Gianluigi; Cordiano, Claudio

doi:10.1093/annonc/mdi207

Cited by 45 publications

(37 citation statements)

References 24 publications

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“…As a result of the good tolerability, the received DI for the three drugs was around 80% of the planned DI. Toxicity data are in keeping with the data reported by Pasini et al [16], in which the same regimen as that used in the present study was used as the induction component of a multimodality treatment for operable cancers of the esophagus and the gastroesophageal junction. Several attempts have been made to improve the tolerability of three-drug regimens including Taxotere administered at lower doses and repeated more frequently.…”

Section: Discussionsupporting

confidence: 88%

Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the treatment of advanced gastric and esophageal cancer: a prospective, observational, single-institution experience

et al. 2011

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The combination of Taxotere (docetaxel), cisplatin, and prolonged-infusion 5-fluorouracil (5-FU) has emerged as an active treatment for advanced gastric cancer. However, the regimen proposed by van Cutsem et al. (J Clin Oncol 24:4991-7, 2006) is associated with significant toxicity and therefore alternative schedules are needed. In the present study, patients with advanced gastric or esophageal cancer received Taxotere 35 mg/m 2 and cisplatin 25 mg/m 2 on day 1, followed by 5-FU 180 mg/m 2 / day as a 7-day prolonged infusion. Drugs were given weekly for 3 consecutive weeks followed by 1 week's rest. Cycles were repeated every 4 weeks. Overall, a total of 110 cycles were administered to 27 patients (median age 63 years, range 40-78 years). The median number of cycles per patient was 4 (range 2-6). Nine partial responses were obtained, resulting in an overall response rate of 33% [95% confidence interval (CI) 16-51], a median time to progression of 6.4 months (95% CI 5.4-7.4), and a median overall survival of 10.7 months (95% CI 6.6-14.8). Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect, in 9 administered cycles (8%); neutropenia was complicated by fever in 2 cycles. Other grade III-IV toxicities observed in [5% of patients were anemia and mucositis.

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Section: Discussionsupporting

confidence: 88%

Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the treatment of advanced gastric and esophageal cancer: a prospective, observational, single-institution experience

et al. 2011

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“…[147][148][149][150][151][152][153][154][155][156][157][158][159][160][161][162][163] In a recent phase I/II study, preoperative chemoradiation with a three drug regimen comprising of docetaxel, oxaliplatin, and capecitabine was safe and effective in patients with locoregional disease. 164 At a median follow-up of 116 weeks, median disease-free and overall survivals were 16 and 24 months, respectively.…”

Section: Preoperative Chemoradiation Therapymentioning

confidence: 99%

Esophageal and Esophagogastric Junction Cancers

Ajani¹,

Barthel²,

Bentrem³

et al. 2011

J Natl Compr Canc Netw

213

153

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“…In phase I and II trials implemented by our group [21][22][23], Siewert type I and II EGJ adenocarcinomas were treated with neoadjuvant CRT; they received 3 weeks of induction chemotherapy alone (5-fluorouracil administered by protracted intravenous infusion plus weekly administration of iv cisplatin and docetaxel) followed by 50.4 Gy of concurrent radiotherapy. Results showed an R0 resection rate of 88% and a pathologic complete response rate of 40%.…”

Section: Neoadjuvant Therapy: Chemotherapy Versus Chemoradiotherapymentioning

confidence: 99%

Western strategy for EGJ carcinoma

et al. 2016

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In this paper, the epidemiological and clinicobiological behavior of esophagogastric junction (EGJ) adenocarcinoma in the West is compared and contrasted to that in the East, and an overview is provided of current therapeutic strategies employed for this type of tumor in Western countries. It is well known that multimodal treatment is the therapeutic standard in locally advanced EGJ adenocarcinoma, but whether neoadjuvant/perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) is the optimal approach is still debated. Neoadjuvant CRT improves local control in locally advanced Siewert type I and II tumors, so it should be considered the treatment of choice. In the subset of these patients with microscopic systemic disease at diagnosis, more intensive exclusive chemotherapy protocols could be of benefit. Therefore, there is an urgent need to identify these patients before planning the treatment. For Siewert type III tumors, perioperative chemotherapy is the standard. While there is general agreement on the optimal surgical approach for Siewert types I and III (a two-field Ivor Lewis operation and a total gastrectomy with distal esophagectomy, respectively), no standard surgical treatment has been defined for Siewert type II tumors. When data from Western series on proximal and circumferential resection margins and on nodal spread in Siewert type II tumors are taken into account, the optimal surgical approach appears to be Ivor Lewis esophagectomy. Whether the extent of esophageal invasion can correctly predict nodal involvement in middle-upper mediastinal stations as a means to restrict indications for transthoracic esophagectomy requires further investigation in the West.

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High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy

Abstract: This schedule represents a feasible treatment and the high pathological response rate is extremely encouraging; the doses found in the last dose-level are the basis for an ongoing phase II study at our institution.

Cited by 45 publications

References 24 publications

Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the treatment of advanced gastric and esophageal cancer: a prospective, observational, single-institution experience

Weekly Taxotere and cisplatin with continuous-infusion 5-fluoruracil for the treatment of advanced gastric and esophageal cancer: a prospective, observational, single-institution experience

Esophageal and Esophagogastric Junction Cancers

Western strategy for EGJ carcinoma

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