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Published on 1 January 2005

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Latest therapies in oesophageal cancer

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Gauri Varadhachary
MD
Assistant Professor
Department of Gastrointestinal Medical Oncology
MD Anderson Cancer Center
University of Texas
Houston, Texas
USA
E:gvaradha@mdanderson.org

Oesophageal cancer is categorised as an aggressive cancer due to poor overall survival rates, which are a consequence of the high risk of both locoregional and distant recurrence. The incidence of oesophageal cancer in the USA was estimated to be 13,900 in 2003, and the mortality for the same year was 13,000.(1) Nevertheless, a small percentage of patients achieve prolonged disease-free survival and a multidisciplinary approach with surgery, chemotherapy and radiation therapy for selected subsets of patients offers the best chance for cure. The median age of onset is 53 years for squamous cell carcinoma and 62 years for adenocarcinoma of the oesophagus.

Pathology
The type of tumour found in the upper to mid-thoracic oesophagus is predominantly squamous cell carcinoma, whereas adenocarcinoma predominates in the distal oesophagus and gastroesophageal (GE) junction.(2) The incidence of adenocarcinoma of the GE junction has risen significantly in the USA, especially in Caucasian men, whereas that of squamous cell carcinoma has slightly decreased. Adenocarcinoma now accounts for at least 75% of all oesophageal cancers in the USA; this is most likely related to an increase in body mass index and subsequent increases in the incidence of Barrett’s oesophagus.

Staging and workup
Workup typically includes history, blood tests (including a complete blood count and chemistry), barium swallow, computerised tomography (CT scan) of the chest and abdomen, and oesophagogastroduodenoscopy. Endoscopic ultrasound (EUS) and (18)F-fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG PET scan) are recommended if there is no evidence of metastatic disease. Bronchoscopy may be considered if the patient has locoregional cancer at or above the carina, and for selected patients with locoregional GE junction cancer a laparoscopic staging of the peritoneal cavity may be warranted. Nutritional status should be addressed early, especially if the patient has dysphagia, and enteral support is preferred, although percutaneous endoscopic gastrostomy (PEG) should be avoided in patients undergoing surgery. A colonoscopy, barium enema (BE) and arteriogram can be considered if colonic interposition is planned.(3) Details of the TNM staging have been published by the American Joint Committee on Cancer (AJCC).(4)

Treatment

Locoregional disease
Treatment of locoregional cancer depends on the site (upper, mid- or lower oesophagus), clinical stage, histology and symptoms.

Patients with carcinoma in situ (Tis) and T1N0M0 are usually offered surgery. Definitive chemoradiation, photodynamic therapy and endoscopic mucosal resection are other options, and a clinical trial is encouraged. Patients with cervical oesophagus squamous cell cancer are candidates for definitive chemoradiation given at 50.4Gy.(5) Patients with cancer involving the upper thoracic oesophagus are offered definitive chemoradiation, surgery, or both, and those with lower thoracic and GE junction (adenocarcinoma) are offered definitive chemoradiation (with salvage surgery, if needed), surgery alone, or both. Preoperative chemoradiation followed by surgery is a common practice pattern in the USA in selected patients. Ajani and colleagues recently published a study with preoperative induction chemotherapy of irinotecan and cisplatin, followed by chemoradiotherapy and then surgery in patients with locoregional carcinoma of the oesophagus or GE junction.(6)

Forty-three patients were evaluated and 39 underwent an R0 resection. The median survival period for all 43 patients was 22.1 months. Patients who achieved a pathological complete response (CR; 11 patients) or pathological partial response (PR; 16 patients; <10% viable tumour in surgical specimen) had a longer median survival than those who achieved less than a pathological partial response (25.6 months vs 18.5 months; p=0.52).

No study has yet been conducted comparing definitive chemoradiation vs preoperative chemoradiation + surgery vs surgery alone, and overall five-year survival rates for surgery alone and definitive chemoradiation are similar (~20%).

Metastatic disease
Patients with metastatic squamous cell and adenocarcinoma of the oesophagus are candidates for chemotherapy, radiation and best supportive care. The survival range is 6–15 months, and current therapies are mainly palliative. Combination chemotherapy with cisplatin and 5-FU, which has been the standard treatment in the USA for a long time, has a partial response rate of 32% in advanced oesophageal cancer.(7)

Over the last decade, novel agents have been introduced, including taxanes, camptothecins and third-generation platinum agent (oxaliplatin). Irinotecan in combination with cisplatin repeated weekly for four weeks, followed by a two-week rest period (recycled every six weeks), has been studied in patients with advanced oesophageal cancer, leading to a response rate of 56% (CR 6%, PR 51%) and a median duration of response of 4.2 months.(8) Docetaxel in combination with cisplatin and 5-FU has been studied in patients with GE junction cancer; the overall response rate on interim analysis was 39% and one-year survival was 44%, with median overall survival of 10.2 months.(9)

The various combination regimens and single-agent chemotherapies used for metastatic oesophageal cancer are detailed in Table 1. Typically, combination chemotherapies provide better response rates than single agents, although without a significant survival advantage. Patient’s performance status should help decide whether the patient is a candidate for palliative chemotherapy.

[[HPE18_table1_34]]

Other palliative options include expandable metal stents, dilatation and percutaneous endoscopic gastrotomy (PEG) tube placement for dysphagia, palliative radiation therapy for bleeding or pain control, and pain control measures with narcotic analgesia.

References

  1. Jemal A, Murray T, Samuels A, et al. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5-26.
  2. Daly JM, Karnell LH, Menck HR. National Cancer Data Base report on esophageal carcinoma. Cancer 1996;78:1820-8.
  3. NCCN practice guidelines for upper gastrointestinal carcinomas. National Comprehensive Cancer Network. Oncology (Huntingt) 1998;12:179-223.
  4. TNM Classification, AJCC/UICC stages 6th edition 2002. Gastroenterol Clin Biol 2004;28:E55.
  5. Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 2002;20:1167-74.
  6. Ajani JA, Walsh G, Komaki R, et al. Preoperative induction of CPT-11 and cisplatin chemotherapy followed by chemoradiotherapy in patients with locoregional carcinoma of the esophagus or gastroesophageal junction. Cancer 2004;100:2347-54.
  7. Bleiberg H, Conroy T, Paillot B, et al. Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer 1997;33:1216-20.
  8. Ilson DH, Saltz L, Enzinger P, et al. Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol 1999;17:3270-5.
  9. Ajani JA, Cutsem E., Moiseyenko, V, et al.Proc Am Soc Clin Oncol 2003:Abs 999.


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