Combined Chemotherapy and Radiotherapy Compared with Radiotherapy Alone in Patients with Cancer of the Esophagus

Herskovic, Arnold; Martz, Karen; Al‐Sarraf, Muhyi; Leichman, Lawrence; Brindle, Jeffrey; Vaitkevicius, Vainutis K.; Cooper, Jay S.; Byhardt, Roger W.; Davis, Lawrence P.; Emami, Bahman

doi:10.1056/nejm199206113262403

Cited by 1,892 publications

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“…The value of chemoradiotherapy for the treatment of unresectable oesophageal carcinoma remains controversial, and only a few clinical studies have been published since the 1980s (Leichman et al, 1984;Leichman et al, 1987;Poplin et al, 1987;Coia et al, 1991;Herskovic et al, 1992;Frorastiere et al, 1993;Poplin et al, 1994). Most patients in these studies had local -regional disease (UICC stage I or II).…”

Section: Discussionmentioning

confidence: 99%

“…Some studies of a continuous irradiation course combined with 5-FU and CDDP indicated that grade 3 and higher leukocytopenia and oesophagitis occurred in 33 -54% and 48 -50% of patients, respectively (Herskovic et al, 1992;Poplin et al, 1994). It is likely that severe leukocytopenia and oesophagitis frequently occurred in a continuous irradiation course.…”

Section: Discussionmentioning

confidence: 99%

“…Recently published results on chemoradiotherapy indicated that it offers various advantages for the treatment of carcinoma of the oesophagus (Frorastiere et al, 1993;Coia, 1994). In a prospective randomised trial by the Radiation Therapy Oncology Group, which compared chemoradiotherapy with radiotherapy alone, the combined-modality arm demonstrated a significant improvement of survival (Herskovic et al, 1992), with a 5-year survival rate of 27%, compared with 0% for radiotherapy alone (Al-Sarraf et al, 1997). With regard to the indications of chemoradiotherapy as a curative treatment for patients with locally advanced diseases, our multicentre study suggested that concurrent chemoradiotherapy was potentially curative even in cases with locally advanced carcinoma of the oesophagus (i.e., T4 and/or M1 lymph node metastasis (LYM) disease) (Ohtsu et al, 1999).…”

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Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus

et al. 2003

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We retrospectively investigated the efficacy and feasibility of concurrent chemoradiotherapy for patients with severe dysphagia caused by oesophageal squamous cell carcinoma. Concurrent chemoradiotherapy was performed in 57 patients with T3 or T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU) 400 mg m À2 24 h À1 on days 1 -5 and 8 -12, combined with 2-h infusion of cisplatin (CDDP) 40 mg m À2 on days 1 and 8. Radiation treatment at a dose of 30 Gy in 15 fractions of the mediastinum was administered concomitantly with chemotherapy. A course schedule with 3-week treatment and a 1 to 2-week break was applied twice, with a total radiation dose of 60 Gy, followed by two or more courses of 5-FU and CDDP. In all, 24 patients (42%) achieved a complete response, and the 3-year survival rate was 19%. Major toxicities were leukocytopenia and oesophagitis, and there were two (4%) treatment-related deaths. In contrast, 22 patients with T3 disease survived longer than 35 patients with T4 disease (P ¼ 0.001); however, the survival rate in 15 patients with M1 LYM disease did not differ significantly from that in 42 patients without M1 LYM disease (P ¼ 0.3545). Our results indicate that definitive chemoradiotherapy is potentially curative for locally advanced oesophageal carcinoma with malignant stricture. The efficacy and survival of patients treated with this regimen are related to the T factor.

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confidence: 99%

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confidence: 99%

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Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus

et al. 2003

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“…Multimodality treatment plays an increasingly important role in the treatment of oesophageal cancer. Chemotherapy with concurrent radiotherapy has been shown to be superior to radiotherapy alone in patients with locoregional disease (Herskovic et al, 1992). However, pre-operative treatment with chemotherapy remains still investigational because a number of randomised studies have provided conflicting results (Kok et al, 1997;Kelsen et al, 1998;Clark, 2000).…”

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Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer

et al. 2002

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In a phase I study we demonstrated the feasibility of a bi-weekly combination of paclitaxel 180 mg m 72 with cisplatin 60 mg m 72 . In this study we further assessed toxicity and efficacy of this schedule in the treatment of advanced cancer of the oesophagus or the gastro-oesophageal junction. Patients received paclitaxel 180 mg m 72 administered over 3 h followed by a 3-h infusion of cisplatin 60 mg m 72 . Patients were retreated every 2 weeks unless granulocytes were 50.75610 9 or platelets 575610 9 . Patients were evaluated after three and six cycles and responding patients received a maximum of eight cycles. Fifty-one patients were enrolled into the study. The median age was 56 years (range 32 -78). WHO performance status were: 0 (19 patients); 1 (29 patients); 2 (three patients). All patients received at least three cycles of chemotherapy and all were evaluable for toxicity and response. Haematological toxicity consisted of uncomplicated neutropenia grade 3 in 39% and grade 4 in 31% of patients. Five patients (10%) were hospitalised, three patients because of treatment related complications and two patients because of infections without neutropenia. Sensory neurotoxicity was the predominant non-haematological toxicity; grade 1 and 2 neurotoxicity was observed in 43 and 20% of patients, respectively. Response evaluation in 51 patients with measurable disease: complete response 4%, partial response 39%, stable disease 43% and progressive disease in 14% of the patients. The median duration of response was 8 months. The median survival for all patients was 9 (range 2 -29+) months and the one-year survival rate was 43%. Four patients who received additional local treatment (two patients surgery and two patients radiotherapy) are still disease free after a follow-up of 20 -29 months. This bi-weekly treatment of paclitaxel and cisplatin is well tolerated by patients with advanced oesophageal cancer. The toxicity profile of this regimen compares favourable to that of previously used cisplatin-and paclitaxel-based regimens. Trials are underway evaluating this bi-weekly regimen in a neo-adjuvant setting.

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“…There is some evidence to support the addition of chemotherapy to radiotherapy in locally advanced disease; in one study, 2 year survival rate was increased from 10% to 38% (Herskovic et al, 1992 …”

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Epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) as neoadjuvant chemotherapy in gastro-oesophageal cancer

Melcher

Mort²,

Maughan³

1996

Br J Cancer

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Combined Chemotherapy and Radiotherapy Compared with Radiotherapy Alone in Patients with Cancer of the Esophagus

Abstract: Concurrent therapy with cisplatin and fluorouracil and radiation is superior to radiation therapy alone in patients with localized carcinoma of the esophagus, as measured by control of local tumors, distant metastases, and survival, but at the cost of increased side effects.

Cited by 1,892 publications

References 18 publications

Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus

Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus

Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer

Epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) as neoadjuvant chemotherapy in gastro-oesophageal cancer

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