A case of gastric cancer with liver metastasis responding to low-dose CDDP/5-FU combination chemotherapy

We reported a case of a 62-year-old female with gastric cancer accompanied by liver, Virchow and paraaortic lymph nodes, and bone metastasis (taken low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) combination chemotherapy). CDDP (10 mg/body/day) was injected on 1-5 days i.v. and 5-FU (500 mg/body/day) was injected i.v. continuously on 1-7 days. This treatment cycle was repeated for 4 weeks. After 4 cycles, liver metastasis disappeared without severe side effects. Primary lesion and Virchow's lymph nodes metastasis were reduced. However, bone and paraaortic lymph node metastasis showed no response. It was considered that low-dose CDDP/5-FU combination chemotherapy was effective for liver and lymph nodes metastasis of gastric cancer in this case.     

A case of bilateral multiple liver metastases with distant lymph node metastases due to rectal cancer successfully treated with hepatic arterial infusion (HAI) of levofolinate (l-LV)/5-fluorouracil (5-FU) and radiotherapy

The patient was a 43-year-old male with bilateral multiple liver metastases, who had undergone high anterior resection for rectal cancer (ss, n 0, P 0, H 3, M (-), stage IV). Hepatic arterial infusion (HAI) of low-dose CDDP (10 mg/body) and 5-FU (250 mg/body), 5 times a week, was ineffective for the liver metastases. Consequently, HAI of levofolinate (425 mg/body) and 5-FU (1,000 mg/body), once a week, was attempted. All metastatic liver tumors diminished apparently with calcification after the treatment (PR). Tumor marker (CA19-9 and CEA) levels decreased to less than one-tenth of the pretreatment levels and stabilized for approximately seven months. Mediastinal lymph node metastases, paraaortic lymph node metastases and tumor thrombus in the inferior vena cava were successfully treated with systemic chemotherapy using levofolinate and 5-FU and/or radiotherapy. Although the liver and lung metastases showed rapid growth, the patient died 2 years after the diagnosis of liver metastases. The liver metastases were well controlled for about 20 months. It is important to select interdisciplinary therapies according to the site of the metastases due to rectal cancer.     

A case of rectal cancer with distant lymph node metastases completely responding to postoperative chemotherapy with levofolinate combined with 5-fluorouracil

The patient was a 58-year-old female who had a cancer of the rectum with multiple lymph node metastases including paraaortic lymph nodes and Virchow lymph nodes. Abdominoperineal resection was performed palliatively. After the operation, weekly bolus of 5-fluorouracil combined with levofolinate was carried out. After 2 courses of chemotherapy, metastases of paraaortic lymph nodes and Virchow lymph nodes completely disappeared upon CT examination. Chemotherapy has continued for 14 months, and she is well and has maintained a complete response for more than 1 year. This case suggests that this combination chemotherapy of LV/5-FU, admitted in Japan, is effective against advanced colorectal cancer.     

A case of advanced gastric cancer with Virchow's and paraaortic lymph node metastases successfully resected after combined chemotherapy of low-dose CDDP and 5-FU

The patient was a 61-year-old woman who had Stage IV advanced gastric cancer with Virchow's and paraaortic lymph node metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 3 courses of chemotherapy, the tumor had decreased remarkably in size and Virchow's metastasis had disappeared. She was considered to have a partial response (PR) and underwent distal gastrectomy. Histopathological examination of the primary tumor revealed that almost all cancer cells existed in the mucosal and submucosal layers; few had infiltrated the serosa. A few paraaortic lymph nodes were positive for metastasis, but a curative resection (Cur B) was performed. The patient received another course of chemotherapy after the operation. Low-dose CDDP and 5-FU therapy was associated with few adverse events in this case, and thought to be effective against advanced gastric cancer.     

A case of rectal cancer with lymph node metastasis (N4) successfully treated with low-dose cisplatin and UFT]

A 65-year-old man was admitted to our hospital due to the swelling of bilateral inguinal lymph nodes and anal discomfort. Sigmoidoscopy revealed a type-1 tumor of the lower rectum which was histologically diagnosed as a poorly-differentiated adenocarcinoma, and inguinal lymph node biopsy showed metastatic adenocarcinoma. An abdominal CT scan revealed swelling of the paraaortic lymph nodes. After a full explanation of the treatment options, the patient chose chemotherapy. Treatment by intravenous infusion of 7.5 mg/body/day of cisplatin for 5 days a week and oral administration of 600 mg/day of UFT was carried out. After 4 weeks of treatment, the primary tumor and swelling of the paraaortic lymph nodes had disappeared, and there was a 61% reduction in the inguinal lymph nodes. Four months later, the primary lesion recurred but vanished again following the same treatment regimen for 6 weeks. The patient has been in good health for over 9 months with no adverse effects from the chemotherapy.     

A case of diffusely infiltrating carcinoma of the sigmoid colon associated with lymphangitis carcinomatosa effectively treated with sequential MTX.5-FU and 5'-DFUR

A 37-year-old man was diagnosed as having a diffusely infiltrating carcinoma of the sigmoid colon associated with lymphangitis carcinomatosa. Sequential methotrexate (MTX).5-fluorouracil (5-FU) therapy with oral administration of doxifluoridine (5'-DFUR) was started. After 9 cycles of the MTX.5-FU therapy (total dose: MTX = 900 mg/body, 5-FU = 7,500 mg/body), radiographic examinations showed a partial response in the primary and pulmonary lesion, and paraaortic lymph nodes. Histological evaluation of the resected specimen by Hartmann's operation showed a grade 2 effect in the primary lesion and metastatic lymph nodes. This chemotherapy was repeated postoperatively. The patient died of pulmonary disease, deteriorating rapidly 60 days postoperatively. Diffusely infiltrating carcinoma of the large-bowel is generally far advanced at the time of diagnosis. The results suggest that sequential MTX.5-FU therapy and oral administration of 5'-DFUR are worth performing in clinical trials for patients with diffusely infiltrating carcinoma of the large-bowel.     

A case of nonresectable scirrhous type gastric cancer treated by hypertensive subselective chemotherapy with pharmacokinetic modulating chemotherapy

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. A 62-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the upper gastric body. Histologic study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography revealed swollen paraaortic lymph nodes and peritonitis carcinomatosa. The patient was diagnosed as having a nonresectable scirrhous type gastric cancer with peritonitis carcinomatosa and paraaortic lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by a subcutaneously implanted port system placed into the thoracic aorta. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as a pharmacokinetic modulating chemotherapy (PMC). After eight courses of treatment of PMC, paraaortic lymph node swelling and ascites decreased. This chemotherapy produced a partial response in the peritonitis carcinomatosa and paraaortic lymph nodes. This chemotherapy was repeated preoperatively. We reconsidered this case to show indications for operation. The patient died suddenly of acute heart failure before the operation. This therapy was considered an effective treatment for nonresectable gastric cancer.     

A case of gastric cancer with paraaortic lymph node metastasis responding to preoperative chemotherapy and surviving 4 years and 4 months after total gastrectomy

A 68-year-old woman was admitted to our hospital because of type 4 gastric cancer associated with paraaortic lymph node metastasis. Considered surgically incurable, she was placed on preoperative chemotherapy consisting of Methotrexate (MTX) 50 mg (day 1), CDDP 10 mg (day 2-6), 5-FU 500 mg (day 1-6) and Leucovorin (LV) 60 mg (day 2-6). Because of severe nausea and leucopenia, she could receive only 1 course of the chemotherapy. CT on January 7, 1997 (5 weeks after the chemotherapy) showed that the gastric wall thickness and the paraaortic lymph nodes swelling had decreased remarkably. She underwent total gastrectomy on January 13, 1997 (pT2, pN2, pM1 (LYM), stage IV, TNM classification). As an outpatient, she was treated with UFT-E 300 mg/day (continuous until the present) and MTX 50 mg (day 1), 5-FU 500 mg (day 1) and LV 60 mg (day 2-3) once two weeks (total 27 cycles). Four years and 4 months after surgery, although peritoneal recurrence was suspected, she has been managed at our outpatient clinic.     

A case of stage IV diffusely infiltrating colon cancer treated by surgical resection and chemoradiation therapy

A 62-year-old male patient presented at the hospital because of left lower abdominal tumor. Based on preoperative examination and biopsy results, he was diagnosed with stage IV diffusely infiltrating colon cancer (scirrhous type) with paraaortic lymph node metastases. He underwent sigmoidectomy with D1 lymph node dissection and received systemic infusion of 5-FU 750 mg and l-LV 300 mg once a week. This chemotherapy produced no change in response in the paraaortic lymph node metastases for a long time. One year later, there were distant lymph node metastases including left inguinal and Virchow's lymph node, and systemic infusion of CPT-11 was performed. In addition, left inguinal lymph node was treated with irradiation therapy (total 50 Gy). The patient died of multiple organ failure 18 months after the operation. It is known that the prognosis in cases of diffusely infiltrating colorectal cancer is extremely poor. However, this case might suggest that intensive therapies with surgery and chemoradiation are useful in maintaining quality of life and improving survival.     

Method of levofolinate.5-FU administration by hepatic arterial infusion therapy for hepatic metastasis from colorectal cancer

Hepatic arterial infusion chemotherapy with levofolinate (l-leucovorin) and fluorouracil regimen was performed using an implanted port system on unresectable hepatic metastasis patients with colorectal cancer. A comparative study was performed on two groups in which the levofolinate was administered arterially or intravenously. Levofolinate 200-250 mg/m(2) was infused for two hours intra-arterially or intravenously, and 5-FU 400-600 mg/m(2) was administered as a bolus in midinfusion. The regimen was repeated weekly for six weeks, followed by no medication for two weeks. Six patients were administered intra-arterially and 7 patients intravenously. The response rate was higher in the group in which levofolinate was given intravenously. The adverse effect was lower in the former than in the latter group. When 5-FU and levofolinate was performed using an implanted port system, it seemed better to administer levofolinate intravenously.     

A case of advanced gallbladder cancer responding to neoadjuvant intra-arterial chemotherapy

The patient was a 52-year-old female who had been diagnosed as advanced gall bladder cancer by various imaging studies. The cancer responded to neoadjuvant intra-arterial chemotherapy and was curatively resected. Since cancer had invaded the median widely, the posterior and the lateral segments of the liver according to CT imaging, neoadjuvant chemotherapy was used. The combination chemotherapy included intra-arterial chemotherapy (CDDP 10 mg + 5-FU 250 mg/day/week x5 times, EPI 10 mg + 5-FU 250 mg/day/week x3 times) through the hepatic artery and oral chemotherapy (UFT 300 mg/day for 106 days). No severe side effects were found during this chemotherapy. Imaging studies after the chemotherapy showed a partial response (PR) and curative resection (hepato-pancreato-duodenectomy with regional lymph nodes dissection) could be performed successfully. She has been disease-free without any sign of recurrence for 18 months after surgery. We conclude that this combination chemotherapy will be useful for advanced gall bladder cancer if the appropriate combinations, dosages, and administration routes are chosen.     

An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection

We encountered a patient with advanced gastric cancer, with Virchow's lymph node metastasis, who subsequently underwent curative resection after neoadjuvant chemotherapy with the newly developed oral anticancer drug, TS-1. The patient was a 67-year-old woman who had a type 2 tumor in the middle third of the stomach, and Virchow's lymph node metastasis, which was diagnosed by fine-needle aspiration cytology; she also had swollen paraaortic lymph nodes. Curative resection was considered impossible, and TS-1 (100 mg/day) was administered for 28 days in one course, mainly in the outpatient clinic. Although grade 2 stomatitis interrupted the therapy on day 21 of the second course and on day 7 of the third course, the type 2 tumor showed marked remission (partial response; PR) and the metastasis in the Virchow's and paraaortic lymph nodes had completely disappeared after the third course (complete response; CR). Eleven weeks after the completion of the TS-1 treatment, total gastric resection with D3 lymph node dissection was performed. Histopathological examination revealed tumor involvement only in the mucosal and submucosal layers of the stomach and the no. 4d lymph node. Most of the tumor was replaced with fibrosis with granulomatous change in the muscularis propria of the stomach and in the no. 3, no. 6, and no. 7 lymph nodes. This may be the first report of a patient with advanced gastric cancer with Virchow's lymph node metastasis who successfully received curative resection following neoadjuvant chemotherapy with a single oral anticancer drug. Received: August 7, 2001 / Accepted: January 28, 2002     

A patient with gastric cancer with para-aortic lymph node metastases surviving for 9 years after effective preoperative chemotherapy and radical operation

A 63-year-old male patient with type 3 advanced gastric cancer was referred to our hospital. Preoperative examination by CT-scan revealed swollen para-aortic lymph nodes and cancer invasion to the pancreas. The patient was treated pre-operatively with intravenous 5-FU, 500 mg/body/day, continuous infusion for 1 week. Immediately after the chemotherapy, the patient underwent total gastrectomy, splenctomy, left-adrenectomy and resection of the body and tail of the pancreas, along with para-aortic lymph node dissection. Microscopic examination revealed that the tumor was a moderately differentiated tubular adenocarcinoma, which displayed invasion to the pancreas with lymph node metastasis up to the level 3 lymph node. Histologically, the effect of preoperative chemotherapy showed a grade 2 effect on the main tumor, but a grade 3 chemotherapeutic effect was observed at the para-aortic lymph nodes. The patient has subsequently remained disease free for 9 years. In this case, it is considered that the preoperative chemotherapy by 5-FU and potentially curative radical operation yielded a good outcome.     

Two cases of gastrointestinal cancers with major responses to sequential methotrexate 5-FU plus 5'-DFUR

We reported 2 patients treated with Methotrexate (MTX)-Fluorouracil (5-FU) sequential therapy combined with Doxifluridine (5'-DFUR). The method of administration was as follows: MTX 60 mg was given intravenously (iv) followed by 5-FU 600 mg iv 2 hours later in colon cancer and 5 hours later in gastric cancer. Leucovorin 20 mg was administered 3 times every 6 hours beginning 6 hours after 5-FU infusion. This cycle was repeated once a week for 5 weeks. 5'-DFUR 1,200 mg was given orally daily and continued after MTX.5-FU therapy. Patient 1 was a 60-yr-old female with recurrent colon cancer developed four years after sigmoidectomy. She was referred to our hospital for further examinations of elevated serum carcinoembryonic antigen (CEA). The enlarged intraabdominal lymph nodes due to recurrence were demonstrated on computer tomography and the chemotherapy was performed as described above. The swelling of lymph nodes showed marked reduction in size and CEA value was normalized. Patient 2 was a 59-yr-old man with advanced gastric cancer accompanied by giant liver metastasis. Both primary and metastatic lesion responded favorably to this regimen. There was no remarkable side effect in either patient. These results suggest that this method is worth performing in further clinical trials for cancer patients.     

A case of locally advanced breast cancer successfully resected after selective intra-arterial chemotherapy

A 25-year-old female with a large tumor on her left breast was examined at our hospital from August, 1999. Ipsilateral supraclavicular, infraclavicular and axillary lymph nodes were swollen. She was diagnosed as having locally advanced breast cancer of stage IIIb by fine needle aspiration cytology. After the administration of docetaxel (60 mg/m2/3 weeks x 3) failed to improve her condition, we changed the treatment to selective intra-arterial chemotherapy with THP-ADR (60 mg/body/day, day 1 & 8, 41 & 48) by Seldinger's method. The target vessels were the internal thoracic, lateral thoracic, thoracodorsal and deep cervical arteries. We also combined 5-FU 500 mg/body div and CPA 500 mg/body i.v. on the same days with intra-arterial chemotherapy. As a result, the main tumor and metastatic lymph node swelling was remarkably reduced (down-staging was obtained). No recurrence was found for 5 months after curative resection.     

Pharmacological study on levofolinate in intraperitoneal leucovorin-5-FU chemotherapy

We report the pharmacological findings on levofolinate after the intraperitoneal administration of leucovorin-5-FU. Levofolinate 300 mg/saline 500 ml and 5-FU 750 mg/saline 500 ml were administered intraperitoneally over 1.5 h. The plasma and intraperitoneal concentrations of levofolinate at 0, 0.5, 1, 2, 4, 8, 22(20) h after the administration were evaluated at 6 points with HPLC analysis. The intraperitoneal levofolinate concentration went up as high as 100 micrograms/ml and remained above 10 micrograms/ml over 8 hours. This suggested that intraperitoneal administration elevated the portal vein and abdominal lymphatic levofolinate levels. Intraperitoneal levofolinate-5-FU is a promising protocol for gastro-intestinal cancers.     

Effects of low-dose FP therapy for advanced gastric cancer cases

The clinical application of low-dose FP therapy has spread rapidly in Japan. We examined the effects of this form of chemotherapy on patients with advanced gastric carcinoma in China. One cycle of this therapy consisted of intermittent infusion of CDDP (10 mg/body/3 hr), followed by intermittent infusion of 5-FU (250 mg/body/6 hr) and suppository administration of tegafur (500 mg) at night for 5 days with 2-day intervals. As a result, a partial response for the primary lesion and lymph nodes was obtained in some cases, 2 of which are described in this paper. No serious side effects were noted, although administration continued over a long period. Our results suggest that neoadjuvant chemotherapy with low-dose FP may be useful as an inductive approach for advanced gastric cancer, and that the regimen can become a standard therapy for gastric cancer.     

A case of recurrent sigmoid colon cancer successfully treated with 5-FU and UFT

A 57-year-old female patient with recurrent sigmoid colon cancer was successfully treated with 5-FU and UFT for 8 years. The patient, with cancer recurrence in the para-aortic lymph nodes, which were palpated in the abdomen, was given oral 5-FU at a daily dose of 200 mg. During the second week of administration, the mass showed a remarkable decrease in size, and complete disappearance was achieved within one month. However, 5 years and 2 months after discontinuation of 5-FU administration, recurrence in the supra-clavicular lymph nodes and para-aortic lymph nodes was recognized. After administration of UFT at a daily dose of 600 mg, complete disappearance of para-aortic lymph node recurrence was observed. At present, the patient is under observation as an outpatient at our hospital. This case suggests the effectiveness of 5-FU and UFT for lymph node metastases of sigmoid colon cancer.     

A case of disseminated tumor from cecal cancer with survival for over 5 years after twice surgical resection and systemic chemotherapy

A 66-year-old man underwent a curative operation for cecal cancer on the 30th of November, 1998. Since his CEA level rose in January 2001, computed tomography (CT) revealed a tumor in the abdomen. He underwent a resection of this tumor and disseminated tumors that were diagnosed during the operation. He received systemic chemotherapy (5'-DFUR 600 mg 3x everyday, CPT-11 80 mg/body div every 2 weeks), but the CEA level rose again in August 2003. He was diagnosed with spleen metastasis and underwent splenectomy. The tumor disseminated in the left diaphragm was also resected. After that, he received systemic chemotherapy (5-FU 500 mg/body/week div, levofolinate calcium 250 mg/body/week i.v.) as an outpatient. Peritoneal carcinomatosis from colorectal cancer with distant metastasis, in general, has no indication for an operation. However, if dissemination is located after a sufficient observation period, its resection may be recommended.     

A case of recurrent colon cancer with urinary bladder, para-aortic lymph nodes, and spleen metastases successfully treated with CPT-11

The patient was a 71-year-old woman with sigmoid colon cancer with urinary bladder invasion, for which sigmoidectomy with D 3 lymphadenectomy and partial cystectomy was performed. After surgery, the patient was started on 4 courses of 6-week systemic chemotherapy (500 mg/m(2) 5-FU and 200 mg/m(2) l-LV weekly). However, 4 months later, CT revealed local recurrence in the urinary bladder and recurrence in the para-aortic lymph nodes and spleen. Therefore, low-dose CPT-11 therapy (40 mg/m(2) once per week) was instituted, which achieved a complete response as revealed by CT for response evaluation 5 months after the start of therapy. Up to the present, after 8 months no recrudescence or recurrent lesions in other organs have been observed. The patient developed mild side effects such as grade 1 nausea, anorexia, and leukopenia, but has a well-maintained QOL.