(Chest. 1999;116:461S-462S.)
© 1999
American College of Chest Physicians
Multimodality Therapy of Esophageal Cancer*
Cameron D. Wright, MD
*
From General Thoracic Surgery, Massachusetts General Hospital, Boston, MA.
Correspondence to: Cameron D. Wright, MD, Massachusetts General Hospital, General Thoracic Surgery, Fruit Street, Boston, MA 02114; e-mail: wright.cameron{at}mgh.harvard.edu
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Abstract
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Multimodality therapy of esophageal cancer has been evaluated in
several clinical trials, with positive results in terms of improved
survival compared with single-modality therapy. A case report is
presented describing the use of paclitaxel in a multimodality regimen
for a patient with a bulky esophageal tumor. In addition, results are
described of a clinical trial in which patients received a
paclitaxel-based regimen as part of multimodality therapy for
esophageal cancer.
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Introduction
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Multimodality
therapy of esophageal carcinoma appears to improve survival. The
addition of chemotherapy (cisplatin and fluorouracil) to radiation
therapy increased survival compared with radiation therapy alone in a
randomized trial reported by Herskovic and
colleagues.1
Walsh and colleagues2
recently
reported that multimodality therapy (cisplatin, fluorouracil, and
radiation therapy) followed by surgical resection improved survival
compared with surgical resection alone. Urba and
associates3
have recently reported that multimodality
therapy (cisplatin, vinblastine, fluorouracil, and radiation therapy)
followed by transhiatal esophagectomy improves survival compared with
transhiatal esophagectomy alone, with an approximate doubling of
survival. However, the optimal multimodality regimen remains unknown.
Paclitaxel is a newer chemotherapy agent with a high response rate in
metastatic esophageal cancer, which also acts as a radiation
sensitizer.4
Our group has recently evaluated the
introduction of paclitaxel in a multimodality regimen in an effort to
improve survival in esophageal cancer.5
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Case Report
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The patient is a 34-year-old previously healthy man
who initially presented with dull, deep chest pain. A cardiac workup
was negative. A barium swallow demonstrated an irregular esophagus. The
patient had slight difficulty eating but denied significant dysphagia.
There was no history of heartburn. He admitted to a 20-lb weight loss.
Esophagoscopy demonstrated diffuse tumor within the thoracic esophagus,
and biopsy specimens revealed a very poorly differentiated esophageal
cancer. A chest CT scan showed a huge bulky esophageal tumor (maximum
diameter, 7 cm) extending from the thoracic inlet to the
gastroesophageal junction. No lymphadenopathy was seen. A bone and
brain scan was negative for metastatic disease. A positron emission
tomographic scan of the chest and upper abdomen demonstrated
significant uptake along the esophagus with no evidence of metastatic
disease.
The patient underwent intensive induction
chemoradiotherapy, which he tolerated well without complication.
Chemotherapy consisted of two cycles of cisplatin, fluorouracil, and
paclitaxel, administered 4 weeks apart. Cisplatin (20
mg/m2) was infused for 1 h on days 1 to 5.
Fluorouracil (800 mg/m2/d) was given as a
continuous infusion on days 1 to 5. Paclitaxel was given for a period
of 3 h as a single infusion (100 mg/m2).
Radiation therapy was concurrently administered in which the initial
volume (gross tumor and elective volume) was treated once a day and a
boost volume (gross tumor) was given as a concurrent boost for 10 days
on a twice daily schedule during chemotherapy administration. A total
of 58.5 Gy was administered to the gross tumor, and the proximal
esophagus and stomach received 45 Gy.
After chemoradiotherapy, repeat CT scans of the chest and abdomen
demonstrated marked reduction in the size of the tumor and showed no
evidence of metastatic disease. A repeat positron emission tomographic
scan demonstrated there was still activity over the esophagus, with no
evidence of metastatic disease. Eighty days after the beginning of
therapy, the patient underwent esophagectomy via an Ivor Lewis
approach. His postoperative course was uncomplicated, and he was
discharged on the eighth postoperative day. His pathology report
demonstrated no evidence of residual cancer in the esophagectomy
specimen. Multiple lymph nodes were replaced by hyaline material,
suggesting that metastatic carcinoma was present before induction
therapy. All resected lymph nodes were free of tumor. The patient
returned to good health and has returned to work. He remains free of
disease 24 months after the initiation of therapy.
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Phase I/II Clinical Trial
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Forty-six patients have been enrolled in our phase I/II paclitaxel
induction protocol. The median age was 61 years, 85% were male, 96%
were white, and 83% had adenocarcinoma. Pretreatment staging
demonstrated that 14 patients were designated T2N0, 4 were T2N1, 15
were T3N0, 11 were T3N1, and 2 were T4N0. Three paclitaxel dose levels
were investigated: 75, 125, and 100 mg/m2. A dose
of 100 mg/m2 was chosen as the dose to continue
the phase II trial because of dose-limiting grade 4 esophagitis at
paclitaxel 125 mg/m2. Four patients had
progressive disease during induction therapy (liver, 2; CNS, 2) and two
patients died during induction therapy. Forty patients were taken to
the operating room, and all 40 underwent resection. Two patients died
postoperatively of ARDS. Thirty-five percent of the patients achieved a
pathologic complete response rate, and 60% were downstaged compared
with their pretreatment staging. Mean follow-up is currently 23 months,
with a median survival of 30 months. The median disease-free survival
is 27 months. One-, 2-, and 3-year survival is 75%, 65%, and 50%,
respectively. Treatment mortality was 8.7%. Longer follow-up will be
necessary to determine whether the enhanced survival justifies the
toxicity of this program.
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References
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Herskovic, A, Martz, K, al-Sarraf, M, et al (1992) Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 326,1593-1598[Abstract]
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Walsh, TN, Noonan, N, Hollywood, D, et al (1996) A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335,462-467[Abstract/Free Full Text]
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Urba, S, Orringer, M, Turrisi, A, et al (1997) A randomized trial comparing surgery (S) to preoperative concomitant chemoradiation plus surgery in patients (pts) with resectable esophageal cancer (CA): updated analysis [abstract 983]. Proc Am Soc Clin Oncol 16,277a
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Ajani, JA, Ilson, DH, Daugherty, K, et al (1994) Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst 86,1086-1091[Abstract/Free Full Text]
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Wright, CD, Wain, JC, Lynch, TJ, et al (1997) Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study. J Thorac Cardiovasc Surg 114,811-816[Abstract/Free Full Text]
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Abstract
Introduction
