Complete Response of Esophageal Cancer Achieved by Combination Therapy with 5-Fluorouracil, Low-Dose Cisplatin, and Radiation: Report of a Case

2 per day, from days 1–5 combined with the daily administration of low-dose cisplatin, 10 mg/m² per day before each fraction of radiation, given as 2 Gy each time, throughout the entire treatment period of 3 weeks beginning on day 1. The benefits of our preoperative chemoradiation therapy included no severe side effects, down-staging and resectability of the tumor, as well as a pathological complete response, which could prolong the survival time. Our experience of this case prompts us to recommend the concurrent daily preoperative chemoradiation therapy for patients with locally advanced esophageal cancer. (Received for publication on June 20, 1997; accepted on Jan. 6, 1998)     

Role of Multiple Scouting Biopsies before Mohs Micrographic Surgery for Extramammary Paget's Disease

Background. Extramammary Paget's disease (EMPD) frequently extends subclinically, resulting in high recurrence rates after surgical excision. Mohs micrographic surgery (MMS) improves cure rates but may require time-consuming reexcision of subclinical extension. A mechanism to estimate the location and extent of subclinical extension would be helpful.
Objective. To describe and evaluate a technique for multiple scouting biopsies before MMS for EMPD.
Method. A retrospective review of patients at Mayo Clinic who had multiple scouting biopsies before MMS for EMPD without dermal invasion.
Technique. The clinical extent of EMPD is identified. The scouting biopsy sites are determined and documented with photographs. The scouting biopsy specimens are sent for permanent sections. The results of the scouting biopsies help guide the extent of the initial Mohs layer. The tumor is cleared with MMS. An additional 1 mm peripheral margin of tissue is usually submitted for permanent sections.
Results. Multiple scouting biopsies were done in five patients. Four of the five patients had at least one true-positive result. At least one true-negative result was obtained in all five patients. Two patients had at least one false-negative result.
Conclusion. Multiple scouting biopsies before MMS for EMPD without dermal invasion can be a beneficial adjuvant technique.
DAVID L. APPERT, MD, CLARK C. OTLEY, MD, P. KIM PHILLIPS, MD, AND RANDALL K. ROENIGK, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.     

The Benefits of Docetaxel Plus Cisplatin and 5-Fluorouracil Induction Therapy in Conversion to Curative Treatment for Locally Advanced Esophageal Squamous Cell Carcinoma

World Journal of Surgery - Definitive chemoradiotherapy (CRT), used for treatment of patients with an initial diagnosis of unresectable locally advanced esophageal cancer, has led to unsatisfactory...     

Prediction of 5-Fluorouracil and Cisplatin Synergism for Advanced Gastrointestinal Cancers Using a Collagen Gel Droplet Embedded Culture

Purpose. The combination effects of 5-fluorouracil (5-FU) and cisplatin (CDDP) are herein reported using a drug sensitivity assay, with a special focus on the induction of apoptosis.Methods. The combination effects of 5-FU and CDDP were examined using in vitro chemosensitivity testing by means of the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in MKN45 and GSS cell lines, and primary gastrointestinal cancer cells ob-tained from 40 patients. Apoptosis was assayed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin neck end labeling (TUNEL) method.Results. The combination of 5-FU with CDDP increased the efficacy of 5-FU 1.16–1.35-fold with the GSS cell line and 1.10–2.01-fold with primary gastric and colorectal cancers when the exposure time was 7 days. In primary tumor cells a synergistic action was noted in 15 of 40 (38%) gastric and colorectal cancers. Both 5-FU and CDDP were found to induce apoptosis in GSS and MKN45 cells, and the number of apoptotic cells increased synergistically after the combined treatment in the GSS cases and showed a correlation with the results of CD-DST.Conclusions. Our findings suggested that the efficacy of the combined treatment with 5-FU and CDDP can be predicted by the in vitro chemosensitivity test and that a synergistic effect might be associated with the induction of apoptosis.     

Extramammary Paget's disease of the perianal region

Objective Perianal Paget's disease (PPD) is a rare entity. The standard treatment for either in situ or invasive extra mammary Paget's disease (EMPD) is surgical excision. Local recurrence and morbidity from surgery, especially in the elderly, can, however, be high. The aim of this article is to review our experience with PPD and question the currently preferred treatment approaches in light of its histopathology and therapeutic outcome. Patients and methods A chart review of our patients with PPD from 1996 to 2002 was carried out to determine their outcome after treatment. Data from review of the literature are presented. Results Five patients with in situ disease (four females, median age 68 years) were diagnosed as having PPD. A complete surgical excision was attempted in 4 patients and the fifth was treated by photodynamic therapy. At present, all patients are alive, two are free of disease, one has persistent disease and two have local recurrence. Conclusion Considering the significant rate of recurrence even after wide local excision, the extent of surgery needed and the good prognosis with long‐term survival, we question whether nonsurgical modalities should be considered in place of surgery as primary treatment for noninvasive PPD, with radical surgery being reserved for failures or invasive disease.     

A Randomized Trial Comparing Postoperative Adjuvant Chemotherapy with Cisplatin and 5-Fluorouracil Versus Preoperative Chemotherapy for Localized Advanced Squamous Cell Carcinoma of the Thoracic Esophagus (JCOG9907)

Background

Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing??that is, before or after surgery??for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Methods

Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival.

Results

We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P?=?0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54?C0.99, P?=?0.04), where the median follow-up of censored patients was 61.6?months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1.

Conclusions

Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.     

复发性阴囊阴茎Paget病18例临床分析

目的:探讨复发性阴囊阴茎Paget病的复发因素、治疗方法和预后。方法:对收治的18例复发性阴囊阴茎Paget病的临床表现、治疗和预后进行回顾性研究,均行组织活检确诊后进行广泛切除术,深达深筋膜,术中冰冻和术后石蜡切片均为切缘阴性,7例淋巴结活检阳性患者均进行淋巴结清扫。结果:全部病例均获得随访,随访时间为6个月～8年,平均34个月。4例因远处转移死亡,其余14例随访期间未见再次复发。结论:对于无转移的复发性阴囊阴茎Paget病患者,局部再行广泛切除术同样是首选治疗,预后良好,对伴淋巴结转移的患者,需行局部淋巴结清扫。     

Alternating Treatment with S-1 Plus Low-Dose Cisplatin and S-1 Alone for Advanced Gastric Cancer

Background  

The aim of this study was to investigate the efficacy and safety of an alternating regimen of S-1 plus low-dose cisplatin and S-1 alone as adjuvant therapy in patients with advanced gastric cancer.     

Photodynamic Therapy for Actinic Keratosis Followed by 5-Fluorouracil Reaction

BACKGROUND: Actinic or solar keratoses are the earliest form of cancerous lesions that are found in sun-exposed areas of the body. Treatment involves eliminating the lesions before they have a chance to progress. Mainstay therapies include curettage, cryosurgery, and topical 5-fluorouracil. A recently Food and Drug Administration-approved regime using photodynamic therapy has also been employed since 2000. OBJECTIVE: To inform physicians of the efficacy and potential inefficiency of this procedure, enabling the assessment of proper placement in the armamentarium. METHODS: This patient underwent photodynamic therapy. She was challenged with 5-fluorouracil 5 weeks after photodynamic treatment. RESULTS: The patient responded well to the photodynamic therapy and also to the challenge with the 5-fluorouracil. CONCLUSION: Did the photodynamic treatment really destroy lesions significantly? What is the mechanism for the response to 5-fluorouracil after such a short period between treatment modalities? If 33% of patients treated with photodynamic therapy require retreatment in 8 weeks, is this modality cost-effective, and what is its place in treating patients? How should this new treatment be implemented in practice? These questions must be seriously assessed.     

Phase I Dose-Escalation Study of Docetaxel,Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma

A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m² DOC plus 70 mg/m² CDDP on day 1 plus 700 mg/m² 5-FU on days 1–5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started.Key words: Docetaxel, Cisplatin, Fluorouracil, Esophagus, Phase ILocally advanced esophageal carcinoma is often refractory to current therapeutic approaches, and its prognosis is grim.^1,2 Patients with unresectable or inoperable disease are usually treated with chemotherapy or chemoradiotherapy.^3,4 Although various chemotherapy regimens are available, esophageal cancer carries a very poor prognosis, with a survival time of less than 8.1 months with current chemotherapies used singly or in combination with 5-fluorouracil (5-FU), vindesine, mitomycin, docetaxel (DOC), paclitaxel, cisplatin (CDDP), irinotecan, vinorelbine, or capecitabine.⁵ 5-FU and CDDP combination therapy (PF) is regarded as standard,⁶ for which the median survival time is reported to be 9.2 months for responders and 5.3 months for nonresponders.⁷In recent years, a new combined chemotherapeutic regimen consisting of DOC, CDDP, and 5-FU (DCF) has received much attention for the treatment of esophageal cancer.⁸ The DCF regimen exploits the strong clinical effects of each component. However, there are few reports describing the use of a combination of DOC, CDDP, and 5-FU (DCF) for esophageal carcinoma.⁹ Therefore, we conducted a phase I clinical trial of a DCF regimen in patients with advanced esophageal carcinoma. Our aim was to determine the recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of DCF combination chemotherapy for patients with esophageal carcinoma. Secondary objectives were to assess treatment-related toxicity and efficacy.     

食管癌细胞MUC1过表达对5-氟尿嘧啶及顺铂化疗效果的影响

目的探讨食管癌细胞MUC1过表达对5-氟尿嘧啶及顺铂化疗效果的影响。方法构建MUC1过表达及稳定沉默食管癌细胞株,建立食管癌细胞裸鼠移植瘤模型;顺铂（8mg／kg,d1,d7）及5-氟尿嘧啶（20mg／kg,d1～d6）腹腔注射,测量肿瘤体积及裸鼠体重,绘制生长曲线及体重曲线;计算肿瘤抑瘤率。结果顺铂与5-氟尿嘧啶均能抑制MUC1过表达食管癌移植瘤的生长,裸鼠体重及肿瘤体积与对照组比较,差异有统计学意义（P〈0．05）,且顺铂的抑制效应更明显（P〈0．05）;在MUC1稳定沉默裸鼠无明显的抑制效应。结论顺铂与5-氟尿嘧啶都能抑制MUC1过表达食管癌移植瘤的生长,顺铂的抑制效应更明显,同时对体重的影响也更明显。     

Randomized Phase II Study to Comparing Docetaxel/Nedaplatin versus Docetaxel for 5-Fluorouracil/Cisplatin Resistant Esophageal Squamous Cell Carcinoma

Purpose: To compare efficacy and safety of dual docetaxel/nedaplatin treatment versus docetaxel alone as second-line chemotherapy for advanced esophageal cancer.Methods: In all, 36 patients with metastatic and/or recurrent esophagus squamous cell carcinoma resistant to first-line chemotherapy (fluorouracil/cisplatin) were recruited from 2011 to 2018 and randomized into two groups. Treatment response and survival were compared between the docetaxel/nedaplatin (60/80 mg/m²/day) group and docetaxel (70 mg/m²/day) group. Treatment was repeated every 3 weeks until tumor progression. Patients were followed up until March 2019 or death.Results: The frequency of Grade 3 or higher adverse events in the docetaxel/nedaplatin group (58.8%) was higher compared with the docetaxel group (26.3%) (P = 0.090). We found a treatment response rate of 52.9% and 36.8% and a median survival of 8.9 and 7.0 months in the docetaxel/nedaplatin-treated and docetaxel-treated group, respectively (P = 0.544).Conclusion: No significant survival advantage was found for docetaxel/nedaplatin-treated patients, although there was an increased frequency of high-grade adverse events compared to docetaxel-treated patients. Because of the limited cohort size, a Phase III study based on our findings is not warranted to assess the clinical impact of docetaxel/nedaplatin treatment. This trial is registered with the University Hospital Medical Information Network (UMIN 000005877).     

A Phase II Trial of a New 5-Fluorouracil Derivative, BOF-A2 (Emitefur), for Patients with Advanced Gastric Cancer

The antineoplastic effects of BOF-A2 (Emitefur), a 5-fluorouracil (5-FU) derivative, in capsule form were assessed in patients with advanced gastric cancer, in a multicenter late phase II study and at 11 different hospitals. The patients were scheduled to receive a minimum of two courses of BOF-A2 orally, with each course of BOF-A2 consisting of 200 mg twice daily for 2 weeks followed by a withdrawal period of 2 weeks. Of the 24 patients entered into the study, the clinical response was able to be evaluated in 21 cases and the toxicity was determined in 23 cases. Eleven (45.8%) patients had been treated previously with other anticancer drugs. There was a 38.1% (8/21) response rate (95% confidence interval 17.3–58.9) with 1 (4.8%) complete response (CR) and 7 (33.3%) partial responses (PR), and these responses continued for over 4 months. In particular, the response rate for the primary lesion was 33.3% (3/9). No change (NC) in the disease was observed in 5 (23.8%) patients, and in 8 (38.1%) the disease progressed (PD). At the time of analysis, the median survival of the responders was 13 months, while that of the NC group was 7 months and that of the PD group was 2 months. The major adverse events consisted of gastrointestinal symptoms, myelosuppression, and skin symptoms, while toxicities of grade 3 or more occurred in 26.1% (6/23). These toxicities all resolved within 1–37 days after discontinuing the drug treatment. Based on the above findings, BOF-A2 is considered to be a promising anticancer drug for patients with advanced gastric cancer. Received: Feb. 23, 2000 / Accepted: July 25, 2000