A case of 5-FU-resistant recurrent colon cancer treated with low-dose CPT-11/CDDP on an outpatient basis

We report a case of recurrent colon cancer resistant to 5-FU, whose QOL and PS has been well maintained with low-dose CPT-11/CDDP administered on an outpatient basis for more than 28 months. A 42-year-old male had lymph node recurrence 27 months after curative resection of colon cancer. He had been administered pharmacokinetic modulating chemotherapy (PMC, oral tegafur/uracil plus fluorouracil infusion) after surgery. Combined treatment with CPT-11 (50 mg/m2)/CDDP (6 mg/m2) was performed on an outpatient basis. Nine months of NC was obtained without any severe side effect. Modified administration of this treatment with 5'-DFUR and TS-1 lead to further maintenance of quality of life and performance status. This case suggests the efficacy of low-dose CPT-11/CDDP for cases of 5-FU-resistant colon cancer in terms of QOL and PS.     

Weekly low-dose CPT-11 and HCFU for advanced colorectal cancer on an outpatient treatment basis

We attempted a new outpatient treatment using weekly low-dose CPT-11 for advanced colorectal cancer patients. A 73-year-old female with para-aortic lymph node metastases from advanced rectal cancer was given outpatient treatment for more than 5 months with weekly low-dose CPT-11 and HCFU. CPT-11 was given intravenously at a dose of 20 mg/m2 on day 1 every week. On days 2-7, she was treated by oral administration of HCFU (600 mg). Her serum CEA level decreased and continued to do so for more than 5 months. The size of the para-aortic lymph node was reduced by approximately 40%. There were no adverse effects except leukopenia (grade 2). These results suggest that weekly low-dose CPT-11 and oral HCFU may be an effective therapy on an outpatient basis in cases of advanced colorectal cancer.     

Four cases of advanced colorectal cancer successfully treated with irinotecan plus 5-fluorouracil and l-leucovorin combination chemotherapy

We successfully treated four advanced colorectal cancers with irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. We diagnosed moderately-differentiated adenocarcinoma of the colon in two patients and of the rectum in two patients. We recognized lymph node metastases in one patient and liver metastases in three patients at the time of operation. After excision for a lesion of the colon or the rectum, all patients underwent a 2-week chemotherapy regimen (CPT-11 100 mg/m2/week + 5-FU 500 mg/m2/week + l-LV 10 mg/m2/week). The effect was PR in all patients. The progressive free survival time was 9.5 months and survival time ranged 5-18 months. Grade 3 diarrhea and leukopenia were seen in one patient. All other adverse reactions were mild (grade 1 or 2). CPT-11/5-FU/l-LV combination chemotherapy appears to be effective for advanced and metastatic colorectal cancer.     

Retrospective study of irinotecan plus fluorouracil and l-leucovorin chemotherapy for advanced and metastatic colorectal cancer

Ten cases of advanced and metastatic colorectal cancer treated with irinotecan plus fluorouracil and l-leucovorin systemic chemotherapy (CPT-11/5-FU/l-LV) were investigated. The 10 patients consisted of 7 males and 3 females with a mean age of 64.3 years. We diagnosed adenocarcinoma of the colon in 2 patients and of the rectum in 8 patients. Five patients had liver and lung metastases, 1 had lymph node metastases, 1 had bone marrow metastases and 3 had recurrence in a pelvic lesion. All patients underwent 3-week chemotherapy regimen (CPT-11 50 mg/m2/week + 5-FU 400 mg/m2/week + l-LV 20 mg/m2/week). Five patients received this regimen as a first-line chemotherapy and the other patients as a second-line chemotherapy after 5-FU/l-LV chemotherapy. The effect was CR or PR in all patients receiving the regimen as a first-line chemotherapy. The progression free survival time was 6.8 months and mean survival time was 10.0 months in the first-line patients. Otherwise, all second-line patients had PD. The suppression of white blood cells (grade 1 or 2) was seen in 4 patients. All patients were able to receive the systemic chemotherapy in the outpatient setting. CPT-11/5-FU/l-LV chemotherapy appears to be an effective first-line chemotherapy for advanced and metastatic colorectal cancer.     

Low-dose CPT-11 against a recurrent rectal cancer--a case report]

We attempted a new regimen of low-dose CPT-11 on a 5-FU resistant recurrent rectal cancer patient with multiple lung metastases and a paraaortic lymph node metastasis. CPT-11 was administered at 25 mg/m2/day x 3/week by intravenous infusion. Serum CEA level decreased gradually with a half time of approximately 4 weeks. The lung metastases almost disappeared and the paraaortic lymph node was also reduced more than 50%. There were no adverse effects except slight alopetia. This treatment could be continued on an outpatient basis. These results suggest that low-dose CPT-11 may be more effective and tolerable than the conventional, CPT-11 therapy.     

Successful downstaging by a low-dose, fractional administration of irinotecan hydrochloride (CPT-11) in combination with cisplatin in peritoneal lavage cytology positive, 5-fluorouracil refractory advanced gastric cancer patients

A 46-year-old Japanese female with advanced gastric cancer with positive peritoneal cytology and who was refractory to methotrexate plus 5-FU sequential chemotherapy received low-dose, fractional irinotecan hydrochloride (CPT-11) in combination with cisplatin. This regimen could be repeated biweekly on an outpatient basis and was well tolerated. After 8 cycles of administration, a negative change in peritoneal cytology subsequently enabled a total gastrectomy, splenectomy, and cholecystectomy with a D3 lymph node dissection. The rationale for a low-dose, fractional administration of CPT-11 in combination with cisplatin is the synergistic antitumor activity obtained through the ability of SN-38 to potentiate cisplatin-induced cytotoxicity, as well as the increased therapeutic efficacy of a protracted CPT-11 administration over more intense treatment schedules. As far as we are aware, this case report demonstrates for the first time that a low-dose, fractional administration of CPT-11 with cisplatin can successfully produce a negative change in peritoneal lavage cytology, and potentiates a R0 resection in a 5-FU resistant advanced gastric cancer patient. This suggests that this combination could be an effective regimen for potentially disseminated, 5-FU resistant patients.     

Two cases of metastatic or recurrent rectal cancer responding to combined chemotherapy of low-dose CPT-11 and 5'-DFUR as second-line chemotherapy

We performed combined chemotherapy of low-dose CPT-11 and 5'-DFUR as second-line chemotherapy in 2 cases of non-resectable metastatic or recurrent rectal cancer. The first patient was a 61-year-old male who had rectal cancer with liver and lung metastases. The second patient was a 76-year-old male who had initial recurrent rectal cancer with multiple liver metastases. Both patients were given first-line chemotherapy of 5-FU + l-LV. CPT-11 was administered at 60 mg/body on day 1, 8 and 15 of a 4-week course by intravenous infusion as outpatient treatment. Furthermore, 5'-DFUR was administered orally at 800 mg/body every day. Consequently, we obtained a decrease in the tumor markers and a reduction of liver metastases in 2 patients after 3 months, Adverse reactions such as myelosuppression and diarrhea were not observed. This treatment could be continued in safety with good QOL on an outpatient basis. These cases suggest that this combined chemotherapy of low-dose CPT-11 and 5'-DFUR may be an effective treatment for non-resectable colorectal cancer in the future.     

A case of highly advanced ascending colon cancer with multiple bone and liver metastases and pleuritis carcinomatosa treated with pharmacokinetic modulating chemotherapy and low-dose CPT-11

A 54 year-old male was admitted for highly advanced ascending colon cancer with multiple bone and liver metastases and pleuritis carcinomatosa. He was treated with pharmacokinetic modulating chemotherapy (PMC) and low-dose CPT-11. UFT (400 mg) was orally administered daily and a 2-hour infusion of l-leucovorin (250 mg/m2/day) with a continuous infusion of 5-FU (600 mg/m2/24 h) was given once a week on an outpatient basis. CPT-11 (80 mg/body/2 h) was administered every 2 weeks. Partial response was obtained in the liver for 6 months and in the primary lesion for 9 months. Significant decrease of pain from the multiple bone metastases was observed for 4 months without severe side effects, which led to an improvement in performance status and quality of life for the patient. He survived more than 11 months after initial treatment. The duration of his stay at home was 288 days, accounting for 83% of the treatment period. This case suggests the efficacy of home anticancer therapy with PMC and low-dose CPT-11 for highly advanced colon cancer in terms of QOL.     

A case of advanced gastric cancer with liver metastasis completely responding to CPT-11+low-dose 5-FU+CDDP chemotherapy

The case was a 54-year-old man with type-3 gastric cancer in the cardia accompanied by multiple liver metastasis. He received combination chemotherapy consisting of CPT-11 (60 mg/body, day 1 and 8)+low-dose 5-FU and CDDP (5-FU 500 mg/body/day and CDDP 5 mg/body/day, day 1-5 and 8-12, continuous infusion) every 3 weeks. The initial 2 courses were administered on an inpatient basis,and further courses as an outpatient. After 7 courses of therapy without severe adverse events, not only primary lesion but also hepatic metastasis disappeared. He has been free from disease for 4 months, and chemotherapy was further continued with TS-1 (100 mg/body, day 1-14)+CPT-11 60 mg/body, day 1, 8), every 3 weeks. CPT-11 in combination with low-dose 5-FU+CDDP can be one of the most effective regimens for unresectable advanced gastric cancer.     

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 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 hepatic metastasis from colon cancer successfully treated with 5-FU, levofolinate (l-LV) and low-dose CPT-11

The patient was a 67-year-old man in whom hepatic metastasis from transverse colon cancer was detected 15 months after transverse colectomy (D2). We treated the patient by systemically administering 2 courses of 5-FU 750 mg/day with l-LV 350 mg/day (once weekly for 6 weeks per course). Assessment of therapeutic effects by CT showed PD in the patient. As a second-line therapy, we treated the patient by systemically administering 3 courses of 5-FU 750 mg/day, l-LV 350 mg/day and CPT-11 40 mg/day x 3 days (once a week for 4 weeks per course). After 3 courses of this chemotherapy, CT examination revealed a reduction in the tumor size of the liver, and CEA levels decreased at the end of this chemotherapy. This chemotherapy also showed no high-grade toxicities. l-LV/5-FU/low-dose CPT-11 seems to be effective for metastatic colon cancer, and safe from the toxicity standpoint.     

A retrospective study of irinotecan plus fluorouracil and l-leucovorin chemotherapy for advanced and metastatic colorectal cancer

We have treated 14 advanced and metastatic colorectal cancers with irinotecan (CPT-11) plus fluorouracil (5-FU) and l-leucovorin (l-LV) combination chemotherapy. The 14 patients consisted of 8 males and 6 females with a mean age of 65 years. We diagnosed adenocarcinoma of the colon in 10 patients and of the rectum in 4 patients. Four patients had liver metastases, five had lung metastases, and one had both, while one had lung and lymph node metastases, two had lymph node metastases and one had a local recurrence. The chemotherapy consisted of CPT-11 100 mg/m(2) div, as a 150-minute infusion, simultaneously l-LV 10 mg/m(2) div, as a 30-minute infusion, followed by 5-FU 500 mg/m(2) iv, as a bolus injection. This treatment was administered weekly for 2 weeks followed by a 2-week rest period and repeated every 4 weeks. All patients received this regimen as first-line chemotherapy. All patients were evaluated for efficacy 1 CR, 2 PR, 9 SD, and 2 PD. The overall response rate was 21.4% with a median time to progression of 8.1 months and a median survival time of 18.6 months. Grade 3 nausea, diarrhea and the suppression of white blood cells were seen in 3 patients, respectively. All other adverse reactions were mild (grade 1 or 2). Except for one patient,residual patients were able to receive the systemic chemotherapy on schedule. CPT-11/5-FU/l-LV combination chemotherapy appears to be effective first-line chemotherapy for advanced and metastatic colorectal cancer.     

A case of metastatic submandibular lymphnode treated successfully with palliative oral (5-FU + PSK) chemotherapy in the elderly

The patient was a 87-year-old woman diagnosed as type 2 advanced colon cancer in the ascending colon. The patient underwent right hemicolectomy. The pathological diagnosis showed poorly-differentiated adenocarcinoma, si, ly2, v1, n0 (0/41) and Stage IIIa. The postoperative course was uneventful, and she was discharged on POD 23. But a left submandibular lymph node enlarged rapidly within two months after the operation. Aspiration cytology of the lymph node indicated poorly-differentiated adenocarcinoma, and she was diagnosed as recurrent colon cancer. Combined chemotherapy of 5-FU (200 mg/day/po) and PSK (3.0 g/day/po) was started as palliative chemotherapy. The metastatic lymph nodes were reduced in size within two months after the treatment. Oral administration of 5-FU+PSK succeeded without serious adverse effects or worsening of quality of life. Ten months later, no recurrence was detected on physical examination or computed tomography. We conclude that palliative oral (5-FU+PSK) chemotherapy is useful for recurrent colon cancer in the elderly because of its excellent safety and effectiveness.     

A case of advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy using CPT-11 plus S-1

Adjuvant chemotherapy for advanced gastric cancer has not yet been established. We report a patient with advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy consisting of CPT-11 and S-1. The patient was a 69-year-old woman diagnosed with large type 3 advanced gastric cancer with esophageal invasion and having No.3 lymph node metastasis (cT3, cN1, cM0, cStage IIIA), treated with 2 courses of CPT-11 plus S-1 as neo-adjuvant chemotherapy. Computed tomography after neo-adjuvant chemotherapy showed improvement of gastric wall thickness and reduction of lymph node metastasis. Subsequently, she underwent an operation. There was no lymph node swelling,so we performed curative surgery consisting of total gastrectomy, splenectomy, cholecystectomy, and D 2 lymph node dissection. Histological diagnosis was pT2 (MP), pN1, pStage II, and estimation of the histological change by chemotherapy was Grade 2. The course after surgery was good, and she was treated by S-1 after discharge. To date, 8 months after surgery, there is no evidence of recurrence. Combination chemotherapy consisting of CPT-11 plus S-1 can be performed safely as a neo-adjuvant treatment, and may be an effective treatment modality for advanced gastric cancer.     

A case of advanced colon cancer with metastases to both the Virchow's and the paraaortic lymph nodes that achieved complete long-term response with levofolinate.5-FU therapy

A 48-year-old woman presented with a tumor in the supra-clavicular fossa. Under a diagnosis of advanced ileocecal colon cancer with metastases to Virchow's and the paraaortic lymph nodes, ileocecal resection was performed. After surgery, the patient was given 5-FU infused continuously at 500 mg/body per day, and levofolinate was dripped intravenously at 100 mg/body over 2 hours for 5 successive days per week. Two cycles were repeated each week. She was then intravenously given weekly modulation chemotherapy consisting of 125 mg/body levofolinate and 500 mg/body of 5-FU for about 5 months on an outpatient basis. Furthermore, the same administration schedule was continued bi-weekly for 1 year and 4 months. As a result, the enlarged paraaortic lymph nodes had completely disappeared by 5 months after administration of levofolinate.5-FU. The Virchow's lymph node metastasis has not been palpable for 11 months. Throughout the period of treatment, there were no severe side effects and as of this writing, no sign of recurrence for 3 years after surgery. A high quality of life has been maintained. In conclusion, this case seems significant from the viewpoint of the complete long-term response to a moderate dose of levofolinate.5-FU therapy and the long duration of administration, which was tolerable with few side effects. Moreover, we identified the presence of TS and DPD using immunohistochemical staining techniques, when both primary tumor and regional lymph nodes were all negative for the stain test. It was suggested that this cancer especially would responded to 5-FU chemotherapy.     

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 case of gastric cancer presenting with obstructive jaundice and responding to biweekly CPT-11 and CDDP combination administration

A 74-year-old man was suffering from Borrmann type 2 advanced gastric cancer with abdominal lymph node metastases and multiple lung metastases. He started to undergo outpatient treatment with oral administration of TS-1. But pyloric stenosis was found after 6 courses of TS-1 chemotherapy, so he underwent palliative distal gastrectomy. TS-1 chemotherapy was continued afterwards, however obstructive jaundice was found. So combination chemotherapy of CPT-11 60 mg/m(2)and CDDP 30 mg/m(2)biweekly was selected as a second-line therapy after PTCD. As no side effects were found, he could be treated on an outpatient basis by CPT-11 60 mg/body and CDDP 30 mg/body biweekly. Four months has passed since the palliative operation, and the PTCD tube was successfully removed. The abdominal lymph nodes had decreased in size and the patient has maintained good QOL. Thus, combination CPT-11 and CDDP therapy could well be a new candidate for a second-line chemotherapy in outpatients.     

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 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.