Clinical investigation
Esophagus
Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer

https://doi.org/10.1016/j.ijrobp.2006.02.013Get rights and content

Purpose: Phase I–II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer.

Patients and Methods: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994–2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival.

Results: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n = 81) or PFT-R (n = 83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%).

Conclusions: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted.

Introduction

The prognosis for patients with locally advanced esophageal cancer remains dismal. Therapies are needed that will improve both local and distant disease control. There has been a significant interest in the use of taxanes. Multiple Phase I–II studies have demonstrated that taxanes have significant activity in patients with locally advanced and metastatic esophageal cancer (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11). In addition to cytotoxic activity, taxanes act as excellent radiation sensitizers, arresting cells in G2/M, the most radiation-sensitive phase of the cell cycle (12, 13, 14, 15). Thus, adding paclitaxel to standard regimens could potentially benefit esophageal cancer patients treated with definitive chemoradiation or tri-modality therapy by improving local and distant control.

Most patients diagnosed with esophageal cancer in the United States will have locally advanced or metastatic disease (16). Despite the relative frequency of this disease, optimal management for patients with locally advanced disease remains controversial. Surgery alone yields 5-year survival rates in the range of 22% (17, 18, 19, 20, 21). Studies employing tri-modality therapy have not consistently demonstrated a statistically significant survival benefit; however, there is a trend toward improved overall survival with the use of tri-modality therapy (17, 18, 19, 20, 21). At Massachusetts General Hospital, in an effort to improve survival for patients with locally advanced disease, we have adopted a tri-modality approach as the standard treatment for patients who are felt to be able to tolerate aggressive therapy. Because most patients experience disease recurrence despite aggressive therapy, we sought to improve survival by investigating paclitaxel in the neoadjuvant setting in a Phase I–II study (1, 2). Our findings suggested a high pathologic complete response (pCR) rate, but there was significant toxicity (1).

This report updates the results of our experience with neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R), and provides the largest reported experience with the use of this three-drug regimen in esophageal cancer. Additionally, we compare these results to our own institutional experience with cisplatin, 5-FU, and radiation therapy (PF-R) in patients with locally advanced esophageal cancer treated during the same time frame. We examine the pathologic response rates, local control, disease-free survival, and overall survival as well as the significant toxicities in patients treated with either neoadjuvant PF-R or neoadjuvant PFT-R at Massachusetts General Hospital between 1994 and 2002.

Section snippets

Patients and methods

This study was approved by the Internal Review Board at Massachusetts General Hospital.

Demographic data

A total of 164 patients with esophageal/gastroesophageal cancer were treated with curative neoadjuvant chemotherapy (PF = 81 or PFT = 83) and radiation therapy between 1994 and 2002. Patients were more likely to have received paclitaxel during the years of the protocol accrual period, and did not receive paclitaxel before initiation of the protocol. After the protocol closed, patients were less likely to have received paclitaxel as part of their regimen, but paclitaxel use did increase again

Discussion

Phase III data demonstrate that the addition of chemotherapy to radiotherapy improves overall survival in esophageal cancer (22, 23). The ideal chemotherapeutic regimen, however, remains controversial. PF has served as the backbone of the chemotherapeutic regimen for many years. Studies of paclitaxel have suggested a synergistic effect with PF and radiation, offering hope of an opportunity to improve survival for patients with esophageal cancer.

Investigators have been encouraged by the

Acknowledgment

We wish to acknowledge Eileen Sharkey, RHIA, CTR, Massachusetts General Hospital Senior Cancer Registrar, for her valuable assistance in data accumulation.

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