Japanese Journal of Clinical Oncology 30:406-409 (2000)
© 2000 Foundation for Promotion of Cancer Research
A Case of Inoperable Esophageal Carcinoma with Hepatic and Nodal Metastases Which Showed a Long-term Survival after Chemoradiotherapy Including Nedaplatin
,+ 1Division of Gastrointestinal Oncology/Gastroenterology, and 2Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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We report a case of metastatic esophageal carcinoma successfully treated with chemoradiotherapy. A 61-year-old man, diagnosed as suffering from advanced esophageal carcinoma with liver and lymph node metastases, was treated with a combination of nedaplatin (90 mg/m2/day, 1 h drip infusion, day 1), 5-fluorouracil (800 mg/m2/day, continuous infusion, days 1–5), and radiotherapy (2 Gy/day, days 1–5, 8–12 and 15–19). The cycle was repeated twice every 5 weeks from July 2, 1997. He achieved a complete response 1 month after finishing two courses of chemoradiotherapy followed by an additional three courses of chemotherapy without radiation. Seven months after the completion of radiotherapy, pericardial effusion with negative cytology was recognized. The effusion was treated by pericardiocentesis and drainage for several days. After drainage, the effusion could be easily managed with diuretics. This patient is still alive with no evidence of disease more than 2.5 years after the initiation of the treatment.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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In loco-regional carcinoma of the esophagus, chemotherapy, mostly a combination of 5-fluorouracil (5-FU) plus cisplatin, together with radiation therapy has curative potential (1,2). However, for patients with metastatic disease, chemotherapy yields few complete responses and thus is unlikely to have any impact on survival (3). Therefore, a standard therapy for metastatic esophageal carcinoma has yet to be established.
Pericardial disease following incidental irradiation of the heart during treatment of thoracic neoplasms is well recognized in the literature. It has been reported generally to occur several months to a number of years after radiation therapy and to be relatively easily managed in most patients (4). In patients with esophageal carcinoma, however, there are only a few reports detailing pericardial disease after radiation therapy.
We report a case of metastatic esophageal carcinoma associated with a pericardial effusion following chemoradiotherapy. Despite having incurable disease and this substantial complication, the patient remains alive with no evidence of disease more than 2.5 years after the initiation of the treatment.
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CASE REPORT |
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A 61-year-old man was referred to our hospital on May 30, 1997, complaining of dysphagia and weight loss of 10 kg over the last few months. On admission, his weight was 58.9 kg. Blood examination showed that the squamous cell carcinoma antigen (SCC) level was 5.4 ng/ml. The Eastern Cooperative Oncology Group performance status (PS) (5) of the patient was 1. He could eat only soft or puréed foods because of the dysphagia. Endoscopic examination revealed an irregular mass with a central ulceration (Fig. 1a). The histology of the biopsy specimen showed moderately differentiated squamous cell carcinoma (Fig. 2). Fluoroscopic examination showed a cancerous lesion, 4.5 cm in length, at the lower portion of the esophagus. Thoracic computed tomographic (CT) scans revealed esophageal wall thickening, while no abnormal findings were seen in the lung and mediastinum. Abdominal CT scans revealed multiple masses, each 1–2 cm in diameter, in the liver (Fig. 3a). In addition, bulky lymphadenopathy, 6 cm in diameter, around the left gastric and the celiac artery was detected (Fig. 3b). These findings led us to the diagnosis of advanced esophageal carcinoma with liver and lymph node metastases. According to the criteria of the tumor-node-metastasis classification of the International Union Against Cancer (6), these findings showed Stage IVB (T3,N1,M1b) disease.
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Chemoradiotherapy was initiated on July 2, 1997, consisting of nedaplatin (90 mg/m2/day, 1 h drip infusion, day 1) and 5-FU (800 mg/m2/day, continuous infusion, days 1–5) along with radiotherapy (2 Gy/day, days 1–5, 8–12 and 15–19) repeated every 5 weeks. The radiation field included both the primary tumor and the bulky abdominal nodes. One month after completion of the two treatment courses with a total radiation dose of 60 Gy, on September 22, 1997, endoscopic examination revealed complete disappearance of the primary tumor, confirmed histologically (Fig. 1b). Abdominal CT scans on October 3, 1997, also documented the disappearance of liver and lymph nodes metastases (Fig. 3c and d). Furthermore, the patient’s serum SCC level had decreased to within the normal range and he became able to take solid food satisfactorily with an improvement of his PS from 1 to 0. An additional three courses of this chemotherapy regimen alone were subsequently administered and finally ended in February 1998. After this treatment series, complete remission of the metastatic esophageal carcinoma continued and the patient remained symptom-free. His weight recovered to 68.1 kg, which was almost the same as before the onset of disease. During the treatment, he had no significant renal or gastrointestinal toxicities such as nausea/vomiting, appetite loss and diarrhea. Transient Grade 3 leukopenia and thrombocytopenia, according to National Cancer Institute Common Toxicity Criteria, were observed, but they recovered without any use of granulocyte colony-stimulating factor or platelet transfusion. The most severe toxicity was esophagitis, which made him eat only semi-solid food. This toxicity had appeared 1 week after the beginning of radiation therapy and lasted until 2 weeks after the end of radiation therapy. He also suffered the complication of pericardial effusion, which appeared to be treatment-related. Pericardial effusion was detected by a follow-up CT scan on March 24, 1998. Although the patient had no symptoms related to this toxicity at that time, echocardiograms showed a large circumferential pericardial effusion. Therefore, pericardiocentesis and catheter drainage were performed. Over several days, serosanguineous fluid (total volume 690 ml) was drained from the pericardium. There were no cancer cells in the pericardial fluid by cytological examination. One month later, the patient complained of dyspnea and when admitted had a large pericardial effusion. He was treated with pericardiocentesis again (total volume 1500 ml) and his symptoms improved. After the second pericardiocentesis, he was treated conservatively with diuretics (furosemide 20 mg/day and spironolactone 25 mg/day) because the effusion was small to moderate and did not affect the patient’s activity or general condition.
This patient remains asymptomatic with no evidence of recurrence by any examination for more than 2.5 years after the initiation of treatment.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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The prognosis of patients with metastatic esophageal carcinoma remains poor. Their median survival ranges between 4 and 8 months (3). For patients with metastatic disease, although cisplatin-based combination chemotherapy provides an objective response rate of 30–40%, complete responses are rarely seen and the duration of response is usually short (3). Cisplatin-based combination chemotherapy is also associated with various toxic effects such as gastrointestinal, renal and neuro-toxicities, which reduce patient’s quality of life. A recent large European study of combined cisplatin and 5-FU in patients with advanced carcinoma of the esophagus found it to be excessively toxic. The authors concluded that no standard chemotherapy could be recommended for patients with advanced esophageal carcinoma (7).
Recently, several platinum analogs have been synthesized and screened in an attempt to develop new antitumor agents as effective as or even more effective than cisplatin but with lower toxicity. Nedaplatin is one such new platinum analog developed in Japan. In previous Japanese studies, this agent showed encouraging potential for treating squamous cell carcinoma in various organs. For carcinoma of the esophagus, a single agent phase II trial reported a 51.7% partial response rate, although the number of patients was small (8). The dose-limiting toxicity in these studies is myelosuppression, particularly thrombocytopenia. However, severe renal and gastrointestinal toxicities occurred less frequently than with cisplatin. The recommended dose and schedule approved for use was 100 mg/m2 as a 1 hour intravenous infusion every 4 weeks (9,10). Preclinical studies have indicated antitumor synergism between nedaplatin and 5-FU (11). We have reported the preliminary results of a phase I/II study combining nedaplatin and 5-FU, repeated every 4 weeks, in patients with untreated metastatic or recurrent esophageal squamous cell carcinoma (12). A complete response was observed in one and partial responses were observed in seven of 16 patients, for an overall response rate of 50%. Renal toxicity was not observed and gastrointestinal toxicity was mild. Based on these results, nedaplatin might be advantageous compared with cisplatin for patients with metastatic esophageal carcinoma who are generally suffering from malnutrition caused by the primary disease. A phase II study of this combination chemotherapy and a phase I/II study adding radiotherapy are now under way in Japan, including at our institution.
Pericardial disease has been reported to be the dominant cardiac complication following incidental irradiation of the heart during treatment of thoracic neoplasms. Stewart et al. pointed out that pericardial disease after radiation therapy is usually associated with an effusion and generally occurs several months to a number of years after radiation therapy, often asymptomatically (4). It is difficult to estimate the incidence of radiation-induced pericardial disease. In Hodgkin’s disease patients, in whom a large heart volume was irradiated, the incidence was reported to be 
8–25% (13–15). In patients with breast cancer, in whom small volumes of the heart were irradiated, the incidence was reported to be 4.5% (16). In esophageal cancer, analyzed by Cwikiel et al. (17), eight patients out of 73 had cytology-negative pericardial effusions. Two of them were treated with pericardiocentesis and one with pericardectomy. The remainder were treated conservatively with diuretics (17). A recent report in patients with Hodgkin’s disease indicated that a total dose to the heart higher than 41 Gy and a dose per fraction higher than 3.0 Gy significantly increased the risk of pericarditis (18). There is a possibility that concurrent chemotherapy enhances the risk of pericarditis, but its contribution is uncertain. There are no reports of pericardial effusion caused by 5-FU (19,20) or nedaplatin (21) alone. According to the literature, the majority of patients with pericardial effusion after radiotherapy can be treated conservatively with or without simple pericardial drainage. A review article also suggested that there were correlations between the total dose or fraction dose of radiation and pericardial disease (4). Although the maximum tolerated dose for heart injury remains uncertain, attention should be paid to this in the follow-up after chemoradiotherapy for esophageal carcinoma.
The present case report documents that combination therapy with nedaplatin, 5-FU and irradiation contributed to long-term complete regression without any significant toxicities except esophagitis. In addition, this therapy has improved the patient’s symptoms. Therefore, we conclude that this regimen may be useful for metastatic esophageal carcinoma. This must be thoroughly evaluated by ongoing clinical trials.
In the light of our experience, a trial of nedaplatin-combined therapy in patients with esophageal carcinoma might be worthwhile. Further studies are warranted to evaluate the combined effects of nedaplatin, 5-FU and irradiation.
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FOOTNOTES |
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+ For reprints and all correspondence: Hajime Sumi, Division of Gastrointestinal Oncology/Gastroenterology, National Cancer Center Hospital East, 6–5–1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. E-mail: hsumi@east.ncc.go.jp
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REFERENCES |
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1 Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326:1593–8.[Abstract]
2 al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, et al. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol 1997;15:277–84.
3 Putnam SB Jr, Rich TA, Forastiere AA. Cancer of the esophagus. In: De Vita VT, Jr, Hellman S, Rosenberg S, editors. Cancer: Principles and Practice of Oncology, 5th ed. Philadelphia: Lippincott 1997;980–1021.
4 Stewart JR, Fajardo LF, Gillette SM, Constine LS. Radiation injury to the heart. Int J Radiat Oncol Biol Phys 1995;31:1205–11.[ISI][Medline]
5 Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–55.[ISI][Medline]
6 Oesophagus. In: Sobin LH, Wittekind Ch, editors. TNM Classification of Malignant Tumors, 5th ed. New York: Wiley–Liss 1997; 54–58.
7 Bleiberg H, Conroy T, Paillot B, Lacave AJ, Blijham G, Jacob JH, 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 Taguchi T, Wakui A, Nabeya K, Kurihara M, Isono K, Kakegawa T, et al. A phase II clinical study of cis-diammine glycolato platinum, 254-S, for gastrointestinal cancers. Gan To Kagaku Ryoho 1992;19:483–8 (in Japanese).[Medline]
9 Ariyoshi Y, Ota K, Wakui A, Majima H, Niitani H, Ogawa, M, et al. Phase I study of (glycolato-0,0) diammine platinum (II) (254S). Proc Am Soc Clin Oncol 1988;7:59.
10 Sasaki Y, Amano T, Morita M, Shinkai T, Eguchi K, Tamura T, et al. Phase I study and pharmacological analysis of cis-diammine(glycolato) platinum (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion. Cancer Res 1991;51:1472–7.
11 Uchida N, Takeda Y, Hojo K, Maekawa R, Sugita K, Yoshioka T. Sequence-dependent antitumour efficacy of combination chemotherapy of nedaplatin, a novel platinum complex, with 5-fluorouracil in an in vivo murine tumour model. Eur J Cancer 1998;34:1796–801.
12 Muro K, Shirao K, Shimada Y, Matsumura Y, Sugano K, Yamada Y, et al. Phase I–II study of nedaplatin and 5-fluorouracil in patients with advanced esophageal cancer. Proc Am Soc Clin Oncol 1999;258a.
13 Carmel RJ, Kaplan HS. Mantle irradiation in Hodgkin’s disease. An analysis of technique, tumor eradication, and complications. Cancer 1976;37:2813–25.[ISI][Medline]
14 Morgan GW, Freeman AP, McLean RG, Jarvie BH, Giles RW. Late cardiac, thyroid, and pulmonary sequelae of mantle radiotherapy for Hodgkin’s disease. Int J Radiat Oncol Biol Phys 1985;11:1925–31.[ISI][Medline]
15 Brice P, Tredaniel J, Monsuez JJ, Marolleau JP, Ferme C, Hennequin C, et al. Cardiopulmonary toxicity after three courses of ABVD and mediastinal irradiation in favorable Hodgkin’s disease. Ann Oncol 1991;2:73–6.
16 Stewart JR, Fajardo LF. Radiation-induced heart disease. Clinical and experimental aspects. Radiol Clin North Am 1971;9:511–31.[ISI][Medline]
17 Cwikiel M, Albertsson M, Hambraeus G. Acute and delayed effects of radiotherapy in patients with oesophageal squamous cell carcinoma treated with chemotherapy, surgery and pre- and postoperative radiotherapy. Acta Oncol 1994;33:49–53.[ISI][Medline]
18 Cosset JM, Henry-Amar M, Pellae-Cosset B, Carde P, Girinski T, Tubiana M, et al. Pericarditis and myocardial infarctions after Hodgkin’s disease therapy. Int J Radiat Oncol Biol Phys 1991;21:447–9.[ISI][Medline]
19 Labianca R, Beretta G, Clerici M, Fraschini P, Luporini G. Cardiac toxicity of 5-fluorouracil: a study on 1083 patients. Tumori 1982;68:505–10.[ISI][Medline]
20 Ensley JF, Patel B, Kloner R, Kish JA, Wynne J, al-Sarraf M. The clinical syndrome of 5-fluorouracil cardiotoxicity. Invest New Drugs 1989;7:101–9.[ISI][Medline]
21 Ota K, Wakui A, Majima H, Niitani H, Inuyama Y, Ogawa M et al. Phase I study of a new platinum complex 254-S, cis-diammine (glycolato)-platinum. Gan To Kagaku Ryoho 1992;19:855–61 (in Japanese).[Medline]
Received April 17, 2000; accepted June 26, 2000.
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