Two patients with recurrent colon cancer who underwent surgery following a combination of irinotecan and UFT

One patient with pulmonary metastasis from colon cancer and one with para-aortic lymph node metastasis were treated with a combination of irinotecan and UFT. Irinotecan (100 mg/m2) was given by 24-hour intravenous infusion on day 1, and UFT (600 mg/day) was given orally on days 3 to 7 and days 10 to 14 of a 2-week course, which was then repeated. In the patient with pulmonary metastasis, the lesions in the lung resolved after 7 courses of chemotherapy. Surgery was performed after 10 courses. The patient with para-aortic lymph node metastasis had a partial response after 4 courses of chemotherapy, and underwent surgery after 6 courses. The only adverse effects were grade 2 myelosuppression and hair loss, none of which were severe enough to require treatment. With this chemotherapy regimen, patients are admitted for two days biweekly for 24-hour intravenous infusion of CPT-11. Thus, most of the treatment can be performed on an outpatient basis. The combination of irinotecan and UFT is expected to be useful for metastatic or recurrent colon cancer.     

A case of advanced colon cancer with para-aortic lymph node metastasis responding greatly to treatment by adjuvant chemotherapy of low-dose CPT-11 on an outpatient basis

We administered an adjuvant chemotherapy of a bi-weekly low-dose CPT-11 + 5-FU on an outpatient basis to a patient with advanced sigmoid colon cancer and para-aortic lymph node metastasis. After 3 months, tumor markers fell to normal levels and the regression rate in the lymph node was over 80%. Throughout the period of treatment, there were no side effects, and there was no sign of recurrence for 6 months. In conclusion, we consider that with low-dose CPT-11 + 5-FU chemotherapy on an outpatient basis, the patient can maintain a high quality of life and show a massive effect, and that this regimen can be used as a first-line chemotherapy for advanced colon cancer.     

A case of huge advanced rectal cancer resected successfully after chemotherapy with mFOLFOX6

The patient, a 75-year-old woman, who was referred to our hospital in April 2010 because of diarrhea and lower abdominal pain. Abdominal CT scan revealed a large tumor, over 8 cm in diameter within the pelvis, and colonoscopy detected rectal cancer. There was no obvious distant metastasis, although invasion to the uterus and regional lymph node metastasis was suspected. After admission, she had been suffering from tumor-accompanying symptoms such as fever, melena, and abdominal pain. Although loop sigmoid colostomy was performed, symptoms were unimproved, and the tumor had grown to 11 cm in diameter. Therefore, chemotherapy(mFOLFOX6)was started. After two courses of chemotherapy, the tumor-accompanying symptoms improved. Six courses of chemotherapy were administered, and subsequent examination revealed shrinkage of the tumor(effect judgment PR). Thirteen days after final chemotherapy, the tumor was successfully resected. Pathological diagnosis of the surgical specimen was tub2, pSI(sigmoid colon), pN0, and Stage II. The surgical margin was completely free of cancer(R0), and the histological effect of chemotherapy was judged as Grade 1b. The patient had received adjuvant chemotherapy with UFT+LV for half a year after discharge. She has been free from any sign of recurrence for 11 months. This case suggests that appropriate preoperative chemotherapy is useful for locally advanced rectal cancer.     

A long-term survival case of advanced sigmoid colon cancer with massive metastases to the para-aortic lymph nodes

We report a long-term survival case of advanced sigmoid colon cancer with massive metastases to the para-aortic lymph nodes. The patient was a 63-year-old male. He underwent sigmoidectomy with D3 + para-aortic lymphadenectomy for advanced sigmoid colon cancer. Histological examination showed a moderately differentiated adenocarcinoma, ss, ly2, v2, n4 (total 30/64, para-aortic lymph nodes 18/39). From 6 months to 4 years after the operation, tegafur/uracil (UFT) was performed as chemotherapy. After 8-year disease-free interval, CT showed solitary mediastinal lymph node metastases. He underwent thoracoscopic mediastinal lymphadenectomy. Histological examination revealed metastases from colon 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 recurrent gastric cancer with lymph node metastasis successfully treated by CPT-11/CDDP therapy

We report a case ofa 76-year-old man suffering from advanced gastric cancer with lymph node recurrence. Distal gastrectomy was performed for gastric cancer with pylorus stenosis in April 2001. Pathological staging was III A(T3, N1, M0, Cur B). He underwent outpatient treatment with oral administration of UFT 400mg/day as postoperative adjuvant chemotherapy, but stopped after two months because of loss of appetite and general fatigue. Partial liver resection(S4/5)was performed for liver metastasis(S4)in June 2002, and S-1 was administered 80mg/day as adjuvant chemotherapy. However, obstructive jaundice was detected for lymph node recurrence in March 2003, and conducted bile duct stent after PTCD. He started to undergo a biweekly combination chemotherapy of irinotecan (CPT-11)60mg/m / 2 and cisplatin(CDDP)30mg/m2. Three months later, the lymph node had decreased in size. We reduced this therapy, extended the interval, and discontinued it after 24 courses due to adverse reactions, such as leucopenia(grade 3)and general fatigue(grade 2). Afterward, he had no recurrence for over 5 years.     

A case of colon cancer with liver metastases and lymph node metastases successfully treated with surgery followed by CPT-11 and 5-FU chemotherapy

A sixty-year-old woman underwent right hemicolectomy and D2 lymph node dissection. However, a solitary liver metastasis and para-aortic lymph node metastasis were detected three months after surgery. Chemotherapy using CPT-11 and 5-FU (civ) was immediately performed. After one course of this regimen, the chemotherapeutic effect was evaluated as a partial response (PR) in the liver metastasis, and as a complete response (CR) in the para-aortic lymph node. There was a massive therapeutic effect without side effects. Two further courses of chemotherapy were performed after changing from 5-FU to 5'-DFUR. Both regions of metastasis (liver and lymph nodes) continue to exhibit CR and the patient is free from any symptoms almost one year after surgery. The authors believe that this regimen is very effective and will contribute quality of life in advanced colon cancer patients.     

A case of recurrent rectal cancer with paraaortic lymph node metastasis treated by FOLFIRI therapy leading to complete response

A 56-year-old woman was referred to our hospital because of melena. After examinations she was diagnosed with rectal cancer. Anterior resection was performed and the final diagnosis was Stage IIIa. She was treated with adjuvant chemotherapy consisting of UFT/Uzel for one year, followed by UFT alone for one year. Two years after the surgery, abdominal CT suggested solitary paraaortic lymph node metastasis. As the patient denied a surgical treatment, mFOLFOX6 chemotherapy was induced. However, the patient developed a grade 3 allergic side effect, FOLFIRI was administered. Six months after the chemotherapy was started, the paraaortic lymph node metastasis had disappeared. After 50 courses, the case was considered to have achieved a clinical CR which has been maintained now. FOLFIRI was effective for recurrent rectal cancer with paraaortic LN metastasis.     

A case of sigmoid colon cancer with metastases of para-aortic lymph nodes treated with curative resection after irinotecan plus 5-fluorouracil and l-leucovorin combination chemotherapy

A 54-year-old woman visited our hospital with a chief complaint of lower abdominal pain and melena. The patient was diagnosed with sigmoid colon cancer using colonoscopy. Abdominal CT revealed metastases to para-aortic lymph node, so our diagnosis was unresectable sigmoid colon cancer. She underwent a transverse colostomy to avoid stenosis. Two weeks after surgery, she underwent a 1-week chemotherapy regimen (CPT-11 80 mg/m(2)/week+5-FU 2,000 mg/m(2)/week+l-LV 250 mg/m(2)/week) modified AIO regimen combined irinotecan for 3 weeks, followed by a 1-week rest interval as one course. Throughout the period of treatment, there was no adverse event, and this regimen has been maintained for 5 courses. After 5 courses of chemotherapy, primary tumor and metastases to para-aortic lymph nodes were remarkably reduced on colonoscopy and abdominal CT. So, she could undergo curative resection. Pathological efficacy was Grade 3, a complete response. This combination therapy may well be useful for advanced colon cancer patients.     

A long-term survival case of rectal cancer with Virchow's lymph node metastasis by multimodality therapy

A 57-year-old man was diagnosed as having advanced rectal cancer that was suspected for a prostatic gland invasion. CPT-11 plus UFT/LV-based chemoradiotherapy (CRT) was administered. A total radiation dose was 50.4 Gy. After completion of CRT, rectal tumor has shrunken, but Virchow's lymph node metastasis was found on PET CT scan. Therefore, the main rectal tumor was resected first, and chemotherapy was then planned. After an abdominoperineal resection, mFOLFOX6 was started. We have stopped mFOLFOX6 after 9 courses because of grade 3 peripheral neuropathy. FOLFIRI was administered thereafter for 27 courses until the confirmation of the shrinkage of the Virchow's lymph node. With a request from the patient, the chemotherapy was stopped for 7 months. Virchow's lymph node has re-grown. We restarted chemotherapy with FOLFOX + bevacizumab regimen. Although the re-grown Virchow's lymph node was unresectable, a tumor in the rectum was resected for a control of local symptom. We, then, introduced a sequential systemic chemotherapy. After that, we could continue the treatment for 38 months without spoiling the QOL. The patient is alive and come to see us as an outpatient.     

Successfully resected an isolated extraperitoneal metastasis of sigmoid colon cancer--a case report

We herein report an extremely rare operative case of an isolated extraperitoneal metastasis of colon cancer. A female patient had undergone a sigmoidectomy for ileus due to sigmoid colon cancer when she was 40 years old. Peritoneal metastasis, 5 mm in diameter, was on the sigmoid colon mesentery and she was histologically diagnosed as Stage IV. She received fluorouracil-based adjuvant chemotherapy for 24 months. Serum CEA increased gradually from 36 months after the operation, and CT scan demonstrated bilateral ovarium tumors. Bilateral oophorectomy was performed at 44 months after the operation. Serum CEA decreased temporarily, but increased again. Serum CEA increased in spite of giving UFT/LV, so we changed to mFOLFOX6 therapy. Serum CEA decreased until it reached to a normal range after 9 courses, and stopped mFOLFOX6 therapy. Four months later, serum CEA increased again and PET-CT demonstrated a 3 cm mass with calcification in pelvic, and accumulation of FDP. Serum CEA decreased until it reached to a normal range after a resection of extraperitoneal mass. A histological examination of the tumor revealed a moderately differentiated adenocarcinoma similar to colon cancer. She has been well without recurrence 77 months after the first operation.     

Two cases of ovarian metastasis of colon cancer

CASE 1: A 45-year-old female underwent sigmoidectomy, simple total hysterectomy and bilateral adnexotomy for sigmoid colon cancer and a right ovarian metastasis in December 2007. As adjuvant chemotherapy, S-1 was conducted for six months. She remains disease-free for 38 months after the surgery. CASE 2: A 61-year-old female underwent simple total hysterectomy and bilateral adnexotomy for bilateral ovarian tumors following the surgery for colon cancer, metastatic liver cancer and gastric cancer in January 2010. As adjuvant chemotherapy, capecitabine was administered seven times. Five months after the last surgery, para-aortic lymph node recurrence was diagnosed. FOLFIRI/panitumumab therapy was maintained. For both of the two cases in immune-staining, CK20 staining was positive, and CK7 staining was negative. Ovarian tumors were diagnosed as metastasis from colon cancer. Ovarian metastasis of colon cancer is a relatively rare event, but a long-term survival case has been reported by multimodality therapy including surgery.     

Two cases of stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy

CASE 1: A 72-year-old man with epigastralgia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed liver metastasis and para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 4 courses of this treatment, the liver metastasis and para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. There has been no recurrence for 16 months postoperatively. CASE 2: A 66-year-old man with anorexia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 9 courses of this treatment, para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. Eight months after the operation, lymph node metastases were confirmed by abdominal CT scan, and he was treated with chemotherapy as an outpatient as of 13 months after the operation. We experienced two cases of Stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy. It was suggested that adjuvant surgery to highly advanced gastric cancer could improve the prognosis of patients.     

A case of unresectable colon cancer responding to oral leucovorin+oral tegafur/uracil

The patient was a 63-year-old man,who first visited our hospital with the chief complaints of left lower quadrant pain and abdominal distension that had developed around November 13, 2004. On close examination, he was diagnosed with sigmoid colon cancer, multiple liver metastasis, and subileus due to a lung metastasis. His operation took place on December 12 of the same year. Intraoperatively, the sigmoid colon was firmly fixed to the retroperitonium, there was a hard node in the pouch of Douglas, and that part of the jejunum was involved. The lesion was judged to be unresectable,and thus loop colostomy, partial jejunectomy and gastrojejunostomy were performed. After the surgery,the patient was treated with 4 courses of therapy with oral Leucovorin (LV, 75 mg) +oral tegafur/uracil (UFT, 400 mg). As a result, the tumor marker levels decreased markedly, the lung metastasis was no longer observed and the liver metastases became smaller. Therefore, a second-look operation was performed on May 30, 2005. This time it was relatively easy to free the sigmoid colon. The node in the pouch of Douglas was no longer observed, and there were only 2 metastatic lesions in the liver (1 each in S 2 and S 6). Sigmoidectomy and partial hepatectomy were performed, and the stoma was closed. The patient made good progress after the operation and was discharged on the 11 th POD. At present he is receiving chemotherapy with UFT+oral LV as an outpatient. As this therapy is relatively easy to perform and imposes only a small burden on patients,we think that it may be effective not only as adjuvant chemotherapy but also as neoadjuvant chemotherapy in some patients.     

Three cases of liver metastasis of colon cancer responding to systemic combination chemotherapy utilizing CPT-11

Though the first choice of treatment for liver metastasis in colon cancer is surgical resection of liver, 30-60% of such patients experience a recurrence of liver metastasis. Even if reoperation is done optimally, the surgical resection of liver metastasis may not be a definitely curative treatment. For cases of liver metastasis from colon cancer that are non-resectable due to multiple liver metastases, other organ metastases (lung, bone, brain etc.), the advanced age of the patient, or other complications (cerebrovascular disease, diabetes mellitus, heart disease etc.), hepatic arterial infusion or systemic combination chemotherapies are selected. In the present paper, we report 3 cases of effective systemic chemotherapy utilizing CPT-11 for liver metastases from colon cancers. The method was UFT + irinotecan (CPT-11), cisplatin (CDDP) + tegafur + CPT-11, UFT + CPT-11 + etoposide (ETP) + pirarubicin (THP). The result obtained was a partial response (PR) in each case. As there were few adverse effects, we could provide treatment during a short-term admission or an outpatient basis. We thus obtained good post-chemotherapeutic QOL, and these regimens may be effective forms of chemotherapies in the future.     

A case report--combination chemotherapy with oral UFT and CPT-11, 5-FU, l-LV by hepatic arterial infusion for multiple hepatic metastasis from sigmoid colon cancer

A 64-year-old woman was diagnosed with multiple hepatic metastases from sigmoid colon cancer. She underwent resection of the colon and catheter insertion into the hepatic artery for arterial infusion in August 2006. She was then treated with postoperative combination chemotherapy consisting of UFT and CPT-11, 5-FU, l-LV. UFT was administered orally at 400 mg/body/day every day and CPT-11 was injected at 100 mg/body/week, 5-FU at 750 mg/body/week, and l-LV at 300 mg/body/week for 8 continuous weeks. After 2 months of the chemotherapy, the metastatic liver tumors disappeared. So hepatic arterial infusion with the same regimens was injected once every month 4 more times. Oral UFT was administered every day. After 6 months of the combined chemotherapy above, we judged the effects of the chemotherapy to be a complete response. Then the chemotherapy was followed by oral UFT only. As severe nausea and vomiting were seen in this patient with an initial dose of 150 mg/body/week of CPT-11 at first, we reduced the dose of CPT-11 to 100 mg/body/week. From then, outpatient care was possible because no severe events were observed. Combined chemotherapy consisting of oral UFT and CPT-11, 5-FU and l-LV by hepatic arterial infusion is suggested to be a new and effective treatment for multiple liver metastases from colorectal cancer.     

A case of lymph node metastasis after 7 years from Hartmann's operation for stage IV sigmoid colon carcinoma

The case was a 49-year-old woman. In 1995, she underwent Hartmann's operation for sigmoid colon carcinoma. Histological stage was IV [se, n4(+), P0, H0, M(-)]. Adjuvant chemotherapy was performed by MMC and 5'-DFUR. After 7 years from the surgery, she had a lumbar pain. CT examination revealed a retroperitoneal tumor-like shadow and Para-aortic lymph nodes were swelling. In 2002, she underwent probe laparotomy. There were massive lymph nodes metastasis, and tumor resection was impossible. Following several systemic chemotherapies such as UFT/CPT-11 and TS-1, the tumor progressed and liver metastasis appeared. After 9 years from the first operation, she is still able to eat and her performance status is 1.     

A case of metastatic colon cancer to paraaortic lymph nodes and liver treated successfully with oxaliplatin combination chemotherapy

A 62-year-old female had been operated for sigmoid colon cancer and liver metastasis. We showed our original guideline of adjuvant chemotherapy for colorectal cancer to the patient. She selected UFT/LV 3 months after operation. Six months after operation,follow-up CT showed a paraaortic lymph node growing to 1.8 cm. We used FOLFIRI regimen for 3 series, but the nodule size did not change. Twelve months after operation, a new metastatic lesion measuring 2.0 cm appeared in the liver and the paraaortic nodule grew to 3.0 cm in size. We used FOLFOX 4 regimen, which had decreased the size of liver metastasis after only 2 series. After 6 series, liver metastasis disappeared completely and the paraaortic nodule was reduced to 1.2 cm. Making a detailed guideline of adjuvant chemotherapy at each hospital is helpful not only for doctors to have more clinical discretion but for patients to have better-informed consent.     

A case of non-curatively resected colon cancer with liver and lymph node metastases treated by TS-1/CPT-11 combination therapy

The patient was a 66-year-old male who had descending colon cancer with multiple liver metastases and paraaortic lymph node metastases. He underwent a left colectomy with lymph node dissection, but the operation resulted in curability C. The serum CEA level before the operation was 205.5 ng/ml. After 2 courses of 5-FU/LV as first-line chemotherapy, this treatment could not be continued due to grade 3 anorexia. As second-line chemotherapy, the patient was treated with daily oral administration of TS-1 (100 mg/day) for 3 weeks. Due to grade 3 anorexia, this treatment could not be continued. Tailored TS-1/CPT-11 (TS-1 80 mg/day from day 1 to day 21, CPT-11 65 mg/m(2) day 1, 15) combination therapy was then chosen as third-line chemotherapy. After 6 courses of combination therapy, the tumor marker (CEA) was decreased and para-aortic lymph nodes could not be detected by computed tomography (CT). Only grade 1 fatigue was noted as an adverse reaction to the treatment. The patient's good QOL was achieved during follow-up over 24 months with the cancer controlled. This case suggests that patients with non-curative resected colon cancer could benefit from TS-1/CPT-11 combination therapy as a second-line or third-line treatment.     

A preliminary study of preoperative chemotherapy combining irinotecan and cisplatin in patients with gastric cancer with unresectable para-aortic lymph node metastases

BACKGROUND: A high response rate has been reported for chemotherapy combining irinotecan (CPT-11) and cisplatin (CDDP) against advanced gastric cancer. The strong anti-tumor activity of this regimen makes it very attractive as a preoperative chemotherapy. We conducted a preliminary study on preoperative chemotherapy with this regimen in patients with unresectable gastric cancer with para-aortic lymph node metastases to evaluate the feasibility of it as a treatment strategy. METHODS: Patients with unresectable para-aortic lymph node metastasis without distant hematogenous metastasis (H0, M0 and M1 LYM) and peritoneal dissemination (P0) were eligible for entry. The preoperative chemotherapy consisted of at least three cycles of CPT-11 (70 mg/m(2)) on days 1 and 15 and CDDP (80 mg/m(2)) on day 15, repeated every 4-6 weeks. Chemotherapy was followed by surgery with extended lymph node dissection in patients who achieved complete or partial responses and whose cancers were judged to be resectable. RESULTS: Six patients were entered into the study. In total, 18 cycles of chemotherapy were performed and five patients received at least three cycles. Objective partial responses were achieved in four patients. The major toxicities in the chemotherapy were neutropenia and diarrhea, but these were clinically acceptable. Four patients underwent surgery after the chemotherapy, and macroscopically complete resections with extended lymph node dissection were achieved in two patients. There were no therapy-related deaths. We found no pathological complete responses, but observed a definite histopathological effect caused by the chemotherapy in surgical specimens. The median survival time of all patients was 12 months. The longest survival without relapse is >6 years from the start of therapy. CONCLUSIONS: We conclude that preoperative chemotherapy with CPT-11/CDDP therapy is feasible in patients with advanced gastric cancer and that the regimen is safe when followed by surgery. Further clinical studies with larger numbers of patients are warranted to evaluate the efficacy of this strategy.