Concurrent Chemoradiotherapy Using Paclitaxel Plus Cisplatin in the Treatment of Elderly Patients With Esophageal Cancer

the ONA take:

Concurrent chemoradiotherapy (CRT) with paclitaxel plus cisplatin may be effective and well-tolerated in elderly patients with esophageal cancer, a study published in the journal OncoTargets and Therapy has shown.

Although concurrent CRT has been considered as the standard treatment option for patients with inoperable or unresectable esophageal cancer, including elderly patients, the efficacy of fluorouracil and cisplatin as a radiosensitizing chemotherapy regimen has only been approximately 25% to 35%. Therefore, researchers sought to retrospectively evaluate the feasibility and efficiency of a concurrent CRT regimen consisting of paclitaxel, instead of fluorouracil, in combination with cisplatin in elderly patients age 70 years or older.

For the study, researchers analyzed data from 82 elderly patients with esophageal cancer who received cisplatin for 3 days plus paclitaxel given for 3 hours, in addition to concurrent irradiation at a total dose of 60 Gy administered in 30 fractions given at the first day of chemotherapy. The study population consisted of 2 patients with stage 1 disease, 23 with stage 2 disease, 49 with stage 3 disease, and 8 with stage 4 disease.

Results showed that with a median follow-up of 20.4 months, the median overall survival and progression-free survival time were 26.9 months and 18.2 months, respectively. Researchers found that 2-year overall survival rates were 76.0% for patients with stage 1-2 cancer and 38.6% for those with stage 3-4 cancer. The 2-year progression-free survival rate was 64.0% and 21.2%, respectively.

In regard to safety, grade 3-4 leukopenia occurred in 30.5% with esophagitis and dysphagia occurring in 8.5% and 6.1%, respectively. One patient died as a result of a fistula.

The findings suggest that large prospective studies should be conducted to confirm the results of this retrospective analysis.

OncoTargets and Therapy
OncoTargets and Therapy

Objective: This study aimed at assessing the efficiency and safety of concurrent chemoradiotherapy (CCRT) using paclitaxel (PTX) plus cisplatin (CDDP) in elderly (age ≥70 years) esophageal cancer patients.
Patients and methods: Between July 2008 and June 2011, 82 esophageal cancer patients aged ≥70 years were retrospectively analyzed. Chemotherapy consisted of CDDP for 3 days plus PTX given for 3 hours. The preplanned total dose of concurrent irradiation with 60 Gy/30 Fx was given at the 1st day of chemotherapy.
Results: The average age for the enrolled patients was 76.41 years (range: 70–87 years), and the clinical stages were stage I (two patients), stage II (23 patients), stage III (49 patients), and stage IV (eight patients). A total of 66 patients finished CCRT on schedule, including 55 (67.1%) patients in whom treatment regimen was not changed, and the clinical complete response was achieved in 29 patients. With a median follow-up time of 20.4 months, the median overall survival (OS) time and progression-free survival (PFS) time were 26.9 months and 18.2 months, respectively. The 2-year OS and PFS rates for stage I–II and III–IV were 76.0%, 64.0% and 38.6%, 21.2%, respectively. Grade ≥3 leukopenia was observed in 25 patients, and the most common nonhematologic toxicity was esophagitis including five and two patients with grade 3 and 4, respectively. Multivariate analysis revealed that clinical stage was a strong factor for OS and PFS.
Conclusion: CCRT using PTX plus CDDP for selected elderly esophageal cancer patients resulted in encouraging survival outcomes and tolerable toxicities. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report.


Keywords: esophageal cancer, elderly, concurrent chemoradiotherapy, paclitaxel, survival, toxicity 

INTRODUCTION

Esophageal cancer remains one of the most fatal cancers worldwide (representing 7% of all gastrointestinal cancers internationally). The overall 5-year survival rate for all patients with esophageal cancer is no better than a mere 20%,1,2 and it is estimated that over 20% of patients with esophageal cancer are diagnosed at an elderly age.3 Traditionally, esophagectomy plays the pivotal role for the treatment of early-stage and localized esophageal cancer, but it is less frequently performed in elderly patients. A series of reports had revealed that postoperative mortality rates in patients aged ≥70 years ranged from 4.5% to 23% and may even reach 60%.4–6 Concurrent chemoradiotherapy (CCRT) has also been considered as the standard treatment option for patients with inoperable or unresectable diseases, for which elderly patients account for a great proportion as established by the landmark results of Radiation Therapy Oncology Group (RTOG) 8501.7 A combination of fluorouracil (5-FU) and cisplatin (CDDP) has also been confirmed as a standard radiosensitizing chemotherapy regimen since then. However, the efficacy of this regimen was only approximately 25%–35%, and the median survival time was no better than 16 months in advanced esophageal cancer patients.7,8 Thus, exploring other potent radiosensitizers and more effective and tolerable anticancer drugs in elderly patients are gaining momentum.

Paclitaxel (PTX), a broad-spectrum cytotoxic drug, is a promising agent against esophageal cancer. Preclinical studies had shown that PTX can enhance radiation sensitivity of tumor cells, potentiate tumor response, and increase the therapeutic ratio of radiotherapy.9 Clinical trials had also revealed that substituting PTX for 5-FU and combining with CDDP had achieved better efficacy in a neoadjuvant and definitive setting for advanced esophageal cancer, and the effective rate was approximately 50%–60% with a more favorable toxicity profile,10–12 which was also validated in our cancer center.13 But, to our knowledge, no specific data have been published regarding the regimes of PTX and CDDP (TP regime) combined with radiotherapy in the setting of CCRT for elderly esophageal cancer patients.

Based on this background, we performed a retrospective study to investigate the feasibility and efficiency of CCRT with PTX and CDDP for elderly esophageal cancer patients treated in our cancer center. We defined an elderly population as persons aged ≥70 years, according to a series of recent studies.3,14–16  

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