A case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP

We report a case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP. A 52-year-old male was diagnosed with type 3 gastric cancer of angulus (poorly differentiated adenocarcinoma) with left neck, Virchow, mediastinal and abdominal lymph nodes metastases. The patient was treated with 5 courses of M-FLP (MTX + 5-FU + LV + CDDP), and the effect of this therapy was PR, but the tumor was chemoresistant to the sixth course of this therapy. After 7 courses of M-FLP, docetaxel (TXT) with low-dose FP (5-FU + CDDP) was administered to the patient as second-line chemotherapy. After 2 courses of TXT with low-dose FP, the gastric cancer and metastatic lymph nodes were remarkably reduced and the effect of this therapy was PR. The toxic events were anemia (grade 2) and leukopenia (grade 3), which were treated with G-CSF. CDDP and 5-FU based regimens are considered as the first-line chemotherapy for metastatic advanced gastric cancer in Japan; however, a second-line chemotherapy has not been established. As in this case, a TXT based regimen is effective and well tolerated therapy as a second-line chemotherapy for metastatic gastric cancer after prior exposure to CDDP and 5-FU.     

A case report of long-term survival of endocrine cell carcinoma of the esophagus with chemo-radiation therapy

The patient was an 84-year-old man, who was diagnosed with cT3N2 (101L, 109L) M0, stage III esophageal cancer. The tumor, immunohistochemically, was stained positive for CD56 and NSE yielding a definitive diagnosis of endocrine cell carcinoma of the esophagus. We selected chemo-radiation therapy (5-FU/CDDP and 2 Gy/day total 60 Gy) for this patient. As adjuvant chemotherapy, 7 courses of chemotherapy with 5-FU/CDDP, was performed. At 8 months from the chemo-radiation therapy, the disease was diagnosed as cCR. But two years later, lung metastasis appeared, so we started chemotherapy with docetaxel/CDDP/5-FU. After 2 courses, lung metastasis was almost disappeared. He has been survived for four years and five months after chemo-radiation. This case suggests that chemo( FP) -radiation therapy and adjuvant chemotherapy could be an effective treatment for endocrine cell carcinoma of the esophagus.     

Resection of esophageal cancer infiltrating the left main bronchus following complete response to preoperative radiochemotherapy--a case report

We report a case of esophageal cancer infiltrating the left main bronchus in which radical esophagectomy with clear surgical margins could be performed after preoperative radiochemotherapy. The patient was a 57-year-old man, who was found to have esophageal squamous cell carcinoma of the middle thoracic esophagus during a work-up of dysphagia. Bronchoscopy revealed an elevated region protruding into the lumen of the left main bronchus. After radiochemotherapy (liniac irradiation + low-dose FP therapy), the esophageal and bronchial lesion became smaller. The case was evaluated as a clinically complete response. Bronchoscopic ultrasonography showed a clear boundary between the membranous portion of the trachea and the esophageal wall. Based on these findings, the lesion was considered resectable and radical surgery, including 3-field lymph node dissection, was performed. The resected esophageal specimen had residual cancer cells in the muscularis propria covered with normal mucosa. However, the patient is currently healthy with no evidence of disease. The indication for surgical resection in cases of esophageal cancer with contiguous spread, and a good response to preoperative radiochemotherapy, is controversial. It is necessary to verify the effectiveness of surgical resection, as a secondary treatment, by accumulating data on cases such as the present one.     

A case of recurrent esophageal cancer with lung metastases successfully treated with docetaxel-combination chemotherapy

We report a case of a 67-year-old woman diagnosed with advanced esophageal cancer. She was treated with chemo-radiotherapy (5-FU/CDDP therapy and irradiation) initially, and primary lesion was well controlled.Two and a half years after first treatment, a chest CT showed multiple lung metastasis, which were confirmed by thoraco-laparoscopy. We chose docetaxel/CDDP combination chemotherapy, because of severe side effects due to the first treatment. After 3 courses, lung metastatic lesions were reduced. The following courses combining docetaxel-nedaplatin were done as ambulatory treatment. These regimens could be one choice for recurrent esophageal cancer, especially FP therapy-resistant or intolerant cases.     

Successful management of the recurrent esophageal cancer following esophagectomy at a different time with combined local treatment of chemoradiotherapy and hepatic arterial infusion chemotherapy

A 63-year-old man who underwent radical resection for esophageal cancer (cStage III)was diagnosed with metastasis of the paraaortic lymph node 5 months after the surgery. He was treated with concomitant chemoradiotherapy (CRT)with low-dose FP(5-FU, CDDP)and 60 Gy of irradiation. The effect of CRT was a complete response. Seven months later, there was a metastasis to the liver(S4). He received systemic chemotherapy(5-FU, ADR, CDDP: FAP), but it was not effective, so hepatic arterial infusion chemotherapy(FAP)was performed. Hepatic artery infusion therapy( 5-FU 1,000 mg/3.5 h x ADR 10 mg/1 h x CDDP 10 mg/1 h)was given for 1 day at an interval of 2 weeks for 18 months. Since ADR reached the maximum dose, hepatic artery infusion of 5-FU(1,000 mg/3.5 h)and CDDP(10 mg/ 1 h)was continued for 14 months at an interval of 4 weeks. The recurrent lesion disappeared completely 9 months after beginning hepatic artery infusion therapy. The patient is alive 69 months after surgery without any evidence of recurrence. Most cases with recurrent esophageal cancer have multiple metastases, and the treatment is mainly systemic therapy. However, in a patient with recurrent tumors at different times, it is possible to achieve a complete response and long-time survival by local treatment with fewer side effects as in this case. Combined local treatments could be the second treatment option after failed systemic chemotherapy for recurrent tumors in patients with esophageal cancer. Further investigations are necessary.     

Case report: a young woman with advanced esophageal cancer showing pathological complete response to neoadjuvant chemotherapy (CDDP, 5-FU and ADM)

A 32-year-old woman was admitted to our hospital with dysphagia. An upper gastrointestinal series revealed Borrmann type 2 esophageal cancer in the lower thoracic esophagus. Because direct invasion of the thoracic aorta was suspected, FAP therapy (CDDP, 5-FU and ADM) was given as neoadjuvant chemotherapy. After completion of two courses, her dysphagia resolved and the tumor shrank by over 90%, so radical surgery was performed. No lesions were found when the resected specimen was examined macroscopically. The only histological change was hyperplasia of collagen fibers in the submucosa, lamina propria and adventitia of the esophagus. No cancer cells and no metastases to the lymph nodes were observed. Because the tumor had completely disappeared, the histological effect of chemotherapy was classified as grade 3, i.e., pathological complete response (PCR). The response to FAP therapy was excellent and no serious adverse events occurred. Therefore, this is one of the treatments that should be actively applied in patients who have advanced esophageal cancer with suspected lymph node metastasis and invasion of other organs.     

A case of recurrent gastric cancer that responded dramatically to docetaxel and 5'-DFUR combination chemotherapy

A 54-year-old man suffering from Borrmann type 4 advanced gastric cancer with pancreatic invasion and paraaortic lymph node metastases underwent a total gastrectomy, which was a radical C operation. From postoperative month 4, he visited our hospital with multiple liver metastases and increased lymph node metastases. After chemotherapy with CDDP and 5-FU, CDDP and UFT was administered on an outpatient basis. The effect of this therapy was PD, therefore, docetaxel and 5'-DFUR combination chemotherapy was performed as second line therapy. After 2 courses of this therapy, the size of liver and lymph node metastases was reduced and the effect of this therapy was PR. The patient has undergone 4 courses of this therapy and is maintaining a clinical PR. It is conceivable that docetaxel and 5'-DFUR combination chemotherapy is useful for patients with advanced and recurrent gastric cancer, even if they had been treated with 5-FU administration as first line therapy.     

Two cases of complete response of primary esophageal carcinoma treated with 5-FU/CDDP as neoadjuvant chemotherapy

CASE 1: A 67-year-old man with lower thoracic esophageal carcinoma, T2N0M0, cStage II, underwent neoadjuvant chemotherapy (NAC) with 5-FU/CDDP. After 2 courses of NAC, radical resection of the esophageal carcinoma was performed. Primary tumor was not palpable, and lymph node swelling was not found in the resected specimens. Pathologic examination of the resected specimens revealed no malignant cells in the esophagus. Histologic effect of the NAC was grade 3. We obtained down-staging of carcinoma in T0N0M0, fStage 0. CASE 2: A 58-year-old man with thoracic esophageal cancer, T3N2M0, cStage III, underwent NAC with 5-FU/CDDP. After 2 courses of NAC, radical resection of the esophageal carcinoma was performed. Primary tumor was not found in the resected specimens. Pathologic examination of the resected specimens revealed only an irregular fibrosis of esophageal wall, and no malignant cells in the esophagus. Two lymph node metastasis and surrounding fibrosis was found. We obtained down-staging of carcinoma in T0N2M0, fStage II. We report two cases of complete response of primary esophageal carcinoma treated with 5-FU/CDDP as neoadjuvant chemotherapy.     

Complete recovery obtained with combined S-1 + CDDP therapy in a patient with multiple lung metastases from esophageal cancer

PURPOSE: There are numerous reports on the subject of effectiveness in radio-chemotherapy with regard to esophageal cancer, suggesting especially the combination therapy of 5-FU + CDDP aimed for recovery. Treatment becomes difficult when distal metastases appear during an adjuvant therapy followed by surgery. Our report here is a case in which a complete recovery was obtained after changing to S-1, a prodrug of 5-FU, in response to multiple lung metastases which appeared during the combined 5-FU + CDDP therapy followed by surgery for esophageal cancer. CASE: The patient was a 71-year-old male. Endoscopy during a physical examination showed a Type 1 tumor 27-30 cm from the anterior teeth. Detailed tests provided a preoperative diagnosis of esophageal cancer: Ut Type 1, T2-T3, N2, MO, IMO. A right thoracolaparotomic subtotal esophagectomy and retrosternal reconstruction were performed. Pathological findings showed well-differentiated squamous cell carcinoma, pT1b (sm), pN1 (106-rec R), pStage II. Postoperative combination of 5-FU + CDDP (day 1-5, 5-FU 500 mg; CDDP 10 mg/body) was started. Because of the appearance of multiple lung metastases after the completion of 3 courses, 2 courses of S-1 + CDDP (S-1 120 mg/body day 1-14; CDDP 5 mg/body day 1-5, day 8-12) were performed. After completing the chemotherapy, CT revealed the resolution of the lung metastases and complete recovery was diagnosed. Following this, a treatment with S-1 alone was continued until the appearance of bone metastases at which time radiotherapy was performed. The treatment is currently ongoing and no recurrence of the lung metastases has been shown. CONCLUSION: There have been numerous reports of the combination of S-1 + CDDP in esophageal cancer for NAC or in inoperable cases. However, our report suggests that this method may be effective in cases of recurrence or distal metastases.     

A case of resection of esophageal cancer infiltrating the left main bronchus following preoperative chemo-radiotherapy and resection of metachronous lung metastasis

We herein report a case of T4 esophageal carcinoma, which was resected after chemo-radiation therapy. In addition, the metachronous lung metastasis was also resected. A 59-year-old female with esophageal carcinoma, which invaded the left main bronchus, underwent chemo-radiation therapy (the combination of systemic chemotherapy of 5-FU/CDDP and external radiation therapy) from January 2004. After the therapy, although the imaging showed a downstaging of esophageal carcinoma, a severe esophageal stricture appeared with ingestion defective. So hyper-alimentation was performed. After the state of nutrition was improved, esophagectomy was performed on March 2004 without a complication. Histopathological study revealed that no viable cells remained. Nine months after esophagectomy, chest CT scan revealed that a solitary pulmonary tumor appeared in S6 of the right. The solitary tumor enlarged gradually. On August 2005, a surgical resection for the solitary pulmonary tumor was performed. Histopathologically, the lesion was compatible for metastasis from esophageal carcinoma. The patient is alive without recurrence more than 23 months after the last surgery.     

A case of long survival of a scirrhous gastric cancer patient with esophageal invasion and peritoneal dissemination through chemotherapy and palliative surgery

We report a case of advanced scirrhous gastric cancer treated by operation and chemotherapy for over four years. The patient was a 54-year-old female who had suffered from gastric cancer with esophageal invasion. She underwent total gastrectomy with D2 dissection. Operative findings revealed peritoneal dissemination, and it resulted in non-curative resection. After surgery, combination chemotherapy with low-dose CDDP administered intraperitoneally and S-1, combination chemotherapy with paclitaxel and 5-FU, and then combination chemotherapy with docetaxel and S-1 were sequentially performed. She also underwent palliative surgery for intestinal obstruction resulting from carcinomatous peritonitis. She achieved long survival with good quality of life(QOL)by multidisciplinary therapy of chemotherapy and surgical operation.     

Clinical development of S-1 (TS-1) for advanced gastric cancer

The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to be the most effective treatment for advanced gastric cancer in the United States, Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently considered to be the first candidate as the standard drug for advanced gastric cancer. S-1 based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes, are expected to yield good results. Above all, S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable frontline standard for patients with AGC. We therefore need to develop new agents and combination chemotherapy regimens to achieve a greater survival benefit in AGC.     

A case of advanced hepatocellular carcinoma with portal invasion resected after treatment by continuous intra-arterial chemotherapy with cisplatin and 5-fluorouracil

A 67-year-old male diagnosed as having inoperable advanced hepatocellular carcinoma with portal invasion was able to undergo resection after continuous intra-arterial chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP). These were continuously administered for 24 hours at doses of 5-FU of 250 mg and CDDP of 5 mg/day, from day 1 to day 5 in a week, repeated 6 times. In additions to the reductions of the levels of AFP and PIVKA-II from 212.6 ng/ml and 16,100 mAU/ml to 11.8 ng/ml and 12 mAU/ml, respectively, the volume of the tumor and the portal invasion were diminished remarkably. As a result, a left extended hepatectomy could be performed. No sign of recurrence was seen during 16 months of follow-up after the operation. Given the above results, continuous intra-arterial chemotherapy with 5-FU and CDDP therapy may be effective for patients with hepatocellular carcinoma.     

Complete response in a case of advanced esophageal cancer treated by combined chemotherapy of TS-1 and CDDP with radiotherapy

A 70-year-old patient with advanced esophageal cancer with invasion to the aorta was treated by combined chemotherapy of TS-1 and CDDP with radiotherapy. TS-1 (80 mg/m2) was administered for 14 days followed by 14 days rest, CDDP (70 mg/m2) was administered by 24 h continuous intravenous infusion at day 8 after the start of TS-1. Radiotherapy (5 days/week) at 2 Gy/day was concurrently started from the beginning of chemotherapy for 3 weeks. After the end of the first course, leukocytopenia of grade 2 and thrombocytopenia of grade 2 were observed. The second course of chemoradiotherapy was suspended for 1 week. After recovery from the toxicity, the second course was started. After the 2 courses of chemoradiotherapy, endoscopic examination with biopsy revealed the disappearance of the esophageal cancer. Combined chemotherapy of TS-1 and CDDP was administered 2 times after chemoradiotherapy. After this therapy, endoscopy and a CT showed a complete clinical response. No severe adverse effects were observed during this therapy. Combined chemotherapy of TS-1 and CDDP with radiotherapy can be effective for advanced esophageal cancer.     

A case of advanced esophageal cancer invaded to the trachea with PCR after preoperative chemoradiotherapy, which relapsed at the time of three years and seven months after resection

A male in his 40s was diagnosed with type-3 advanced esophageal cancer in the upper thoracic and cervical esophagus, which invaded to the trachea. We administered a low-dose FP combination therapy (5-FU and CDDP) along with 40 Gy radiotherapy. This chemoradiotherapy reduced the esophageal tumor significantly, and then we performed subtotal esophagectomy. Histological examination of the resected specimens revealed no residual cancer cells in the primary lesion or regional lymph nodes. No recurrence had occurred for about three years and seven months after the operation. However, CT revealed that the patient had the signs of recurrence (bone and lung), and finally he died four years and eight months after the operation. Preoperative chemoradiotherapy is potentially effective for advanced esophageal cancer invaded to adjacent organs. Although chemoradiotherapy yielded a complete response in our case( an advanced esophageal cancer patient), a patient follow-up is necessary because a recurrence may occur along the way.     

A case of advanced esophageal cancer with extensive lymph node metastases successfully treated with multimodal therapy

Advanced esophageal cancer patients with extensive lymph node metastases show extremely poor prognosis and the long-term outcome is poorer with the involvement of more lymph nodes. We report here a long-surviving case of advanced esophageal cancer with histologically 34 lymph node metastases, in which surgical resection with three-field lymphadenectomy followed by adjuvant chemotherapy and radiotherapy was performed. A 53-year-old male was diagnosed as advanced middle esophageal cancer with multiple regional lymph node metastases such as paraesophageal, pretracheal, tracheobronchial and bifurcational lymph nodes and three intramural metastatic lesions. Subtotal esophagectomy with three-field lymphadenectomy was performed for the tumor. Histopathologically, the tumor was poorly differentiated squamous cell carcinoma and 34 lymph nodes including ligamentum arteriosum lymph nodes and pretracheal lymph nodes were proved to be metastatic. Numerous tumor cells were found in the lymphatic vessels near the metastatic lymph nodes. Chemotherapy [3000 mg of 5-fluorouracil (5-FU), 50 mg of cisplatin (CDDP) and 30 mg of methotrexate (MTX)] was administered in two courses, followed by radiation therapy (field size 21 x 20 cm in mediastinum, 10 MV X-rays, 2 Gy/fr, 5 fr/week, total 46 Gy). Subsequently, 1000 mg of 5-FU and 200 mg of CDDP were administered every 3-4 months without any significant toxicities. The patient has been alive and well without recurrence for 5 years following operation. For treatment of advanced esophageal cancer with extensive lymph node metastases, a wide resection of the tumor and regional lymph nodes should be performed, followed by adjuvant chemotherapy and radiotherapy.     

A curative resected case of pathological complete response of esophageal carcinoma treated with 5-FU/CDDP as neoadjuvant chemotherapy

A 56-year-old man with advanced esophageal carcinoma and lymph node swelling of abdomen (cStage III) underwent neoadjuvant chemotherapy (NAC) with 5-FU/CDDP. The side effect was stomatitis of grade 2. Primary tumor and lymph node swelling revealed remarkable effectiveness after 2 courses of NAC. Esophageal carcinoma was not found by endoscopy. Reduction of the lymph node was slight, however, radical resection of the esophageal carcinoma was performed. Pathologic examination of resected specimens revealed no malignant cells in the esophagus, and no metastasis of lymph node (Effect grade 3). Thus, we found NAC to be markedly effective for primary tumor and lymph nodes of esophageal carcinoma, and a radical operation was performed.     

The evaluation of gastric cancer sensitivity to 5-FU/CDDP in terms of induction of apoptosis: time- and p53 expression-dependency of anti-cancer drugs

Clinical in vivo and in vitro studies have revealed pronounced gastric cancer activity using the combination of 5-fluorouracil (5-FU) and cisplatin (CDDP). In addition, the combination of 5-fluorouracil plus cisplatin (FP treatment) possesses synergistic cytotoxicity against gastric cancer. Sensitivity of two gastric cancer cell lines to anti-cancer drugs, 5-fluorouracil (5-FU) and/or cisplatinum (CDDP), was evaluated by use of either flow cytometric analysis (FACS) or morphological observation in terms of induction of apoptosis. In morphological observation, a new experimental technique was used in which cancer cells were distributed in thin collagen gel as one or two cell layers, and cultured with anti-cancer drugs. Thereafter, cells were stained with fluorescent Hoechst 33258 (Ho) and photographed, then stained with hematoxylin and eosin (H&E) and photographed again. Cell death patterns were determined by combining observations of Ho- and H&E-stained cells. While combined administration of 5-FU and CDDP did not induce apoptosis of MKN-28 (mutant-type p53), apoptotic cells were markedly observed in the case of MKN45 (wild-type p53). In addition, consecutive administration of CDDP for 3 h and 5-FU for 21 h effectively induced apoptosis of MKN45. These results indicated that the type of p53 expression in cancer cells could be a promising factor in predicting response to FP therapy and the administration of CDDP prior to 5-FU may be more effective in inducing apoptosis of gastric cancer cells with wild-type p53 expression. These data may provide evidence to support the idea that p53 expression is related to multidrug resistance (MDR) in FP therapy of gastric cancer cell lines.     

A case of advanced esophageal cancer with liver metastases: efficacy of combination therapy of docetaxel/cisplatin/5-FU

The combination chemotherapy with docetaxel/CDDP/5-FU(DCF)for head and neck squamous carcinoma(SCC) has been widely accepted. It seems quite natural that DCF therapy is expected to be equally effective against esophageal SCC because of their histological similarity. In this report, we present a case of unresectable advanced esophageal SCC with multiple liver metastases which showed remarkable regression by DCF therapy, with relatively slight adverse effects. The patient was a 46-year-old female, who underwent upper gastrointestinal fiber-optic endoscopy for dysphasia and was diagnosed to have upper middle thoracic esophageal SCC. Abdominal CT scan showed multiple liver metastases with para-aortic lymph node involvement. The clinical stage diagnosis was T3N4M1, Stage IVB, obviously non-resectable far-advanced esophageal SCC. Systemic chemotherapy with DCF was started as the initial treatment. The chemotherapy regimen was as follows. 5-FU 500 mg/m(2) was administered as continuous intravenous infusion through day 1 to 5, while docetaxl 60 mg/m(2) and cisplatin 50 mg/m(2) were given intravenously on day 2. Each course was followed by a 23-day drug-free period, and the entire course was repeated every 28 days. Ten cycles of this DCF chemotherapy were carried out. After 4 cycles, primary lesion was judged as complete response(CR)by endoscopy. After 8 cycles, the liver metastases were judged as CR and para-aortic lymph nodes showed a partial response(PR)by CT scan. After 10 cycles, all we could detect was a small local recurrence of the primary tumor, which was then treated with chemoradiotherapy at the outpatient clinic. Until this writing, we added 2 more cycles of DCF therapy for the recurrent para-aortic and inguinal lymph node metastasis. Three years have passed from her first visit, and the patient is still in a stable disease state. The adverse effects were grade 3 at most in both hematological and non-hematological toxicity. We conclude that DCF therapy is potentially very effective for advanced esophageal SCC.     

Chemotherapy with low-dose CDDP and continuous 5-FU for the treatment of advanced gastric cancers]

INTRODUCTION: 5-fluorouracil (5-FU) has been widely used for the treatment of gastrointestinal cancers. On the basis of recent findings, low-dose Cisplatin (CDDP) and continuous venous infusion of 5-FU have shown additive or synergistic antitumor effects in experimental models. We evaluated clinical effects of low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gastric cancers. PATIENTS AND METHODS: In December 1993 and June 1998, 52 patients with advanced gastric cancer were entered in this study. Patients were considered eligible if they had a bidimensionally measurable tumor. 5-FU (160 mg/m2/day) was continuously infused over 24 hours using an implantable port, and CDDP (3 mg/m2/day) was infused for half an hour. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest every four weeks according to response and tolerance. RESULTS: Low-dose FP therapy was given 44 patients (85%). The response rate was 65.9% and median survival time was 249 days. The responder group showed good survival compared with the non-responder group. The regimen was tolerable, and the most common toxicity was anorexia (40.3%). Three patients suffered from grade 3 anorexia, leukopenia and mucositis. On the other hand, renal dysfunction occurred in 50% (two of four patients administered over 1,000 mg CDDP). These results raise the possibility that the dose-limiting factor of low-dose FP therapy may account for the total dosage of CDDP. CONCLUSION: Low-dose FP therapy promises to be effective in the clinical management of advanced gastric cancer.