Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D01061 (CPT-11)
 1,899 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported the results of phase I study with CPT-11 and S-1 (IRIS) in advanced gastric cancer (AGC) patients at ASCO 2002. Now I present an outline of this phase I/II trial. A combined treatment of IRIS (CPT-11 + S-1) was given to the AGC patients who had not received prior chemotherapy. S-1 was orally administered twice a day for 14 days, and CPT-11 was administered as a 90-minute intravenous infusion on days 1 and 15. This schedule was repeated every 4 weeks. Fifteen patients were registered in this phase I study and 9 patients were added in this phase II study. Non-hematological toxicities were almost classified as grade 2 or lower, except for grade 3 nausea and grade 3 dermatitis of level 2. These adverse events were manageable by administering anti-emetic drugs and a drug rest. As for hematological toxicities, grade 4 neutropenia occurred with one patient at level 1 and level 2 in phase I. And grade 4 neutropenia occurred with four patients at level 2 in phase II. However, they recovered after the drug rest, and we could continue the administration based on the standard dose modifications. These side effects were tolerable, and the overall response rate was 54.2%. MST of this regimen is 581 days. The IRIS treatment is effective and tolerable for outpatient treatments.
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PMID:[Irinotecan plus oral S-1 in patients with advanced gastric cancer-biweekly IRIS regimen]. 1689 76

We report a successful case of chemotherapy accompanied with grade 4 adverse events for unresectable advanced gastric cancer. A 73-year-old man was admitted to our hospital with complaint of abdominal pain in July 2007. The detailed examination had revealed advanced gastric cancer, lymph node metastasis, and multiple hepatic metastases. Performance status (PS) was level 0, and oral intake of medications was possible. Combined therapy with S-1 and CPT-11 (IRIS regimen) was performed from August as the first-line therapy. As a consequence of first course, grade 4 hematological adverse events (AEs) appeared and an urgent hospitalization was required. With whole body supportive care against grade 3 non-hematological AEs, which were diarrhea, anorexia, and fatigue, G-CSF, the broad-spectrum antibiotic were administered at the clean-room. After 1 course, cyto-reductive change was confirmed at the primary lesion and hepatic metastases. We continued the same regimen with dose reduction (S-1: 2 level dose down, CPT-11: 10% dose down). Although the regression of hepatic metastases was seen, we repeated the dose reduction of CPT-11 and the dose down level was reached to 40% for prolonged grade 2 neutropenia. After 6th courses, complete responses at primary lesion, lymph node, and hepatic metastases were achieved. The patient has received the same regimen of 9th course continuously as an outpatient, and CR has been maintained.
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PMID:[A case of unresectable advanced gastric cancer successfully treated with continuous S-1 + CPT-11 chemotherapy accompanied by dose reduction against grade 4 hematological adverse event]. 1910 23

The patient was a 68-year-old male who had advanced rectal cancer with aortic bifurcation lymph node metastasis, who was given neo-adjuvant chemotherapy by IRIS, a combination of S-1 80 mg/m(2)/day (2-week administration and 1-week rest) and CPT-11 100 mg/day (day 1, 15). After 2 courses of this neo-adjuvant chemotherapy, a complete response (CR) was noted by CT scan and endoscopy. We were able to conduct a super low anterior resection of the colon and rectum. Postoperative histopathological examination of the resected rectum and lymph nodes showed only the spot of residual cancer tissue and the degeneration of cancer cells and fibrosis, revealing that the operation had been conducted radically. The changes from neo-adjuvant chemotherapy were judged to be Grade 2. And we could thus conduct the radical operation. The treatment was completed without adverse events. IRIS therapy can be an effective method as neo-adjuvant chemotherapy.
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PMID:[A case of advanced colon cancer treated with preoperative chemotherapy (IRIS) leading to clinical complete response]. 1969 81

In a patient with multiple liver metastases of colorectal cancer whose tumor response had been achieved by 5-FU hepatic arterial infusion, a catheter for arterial infusion chemotherapy was occluded resulting in re-elevation of tumor marker levels. For this reason, a second-line IRIS therapy using S-1 and CPT-11 was started. IRIS therapy reduced tumor marker levels to a degree greater than that of previously achieved with 5-FU hepatic arterial infusion, and a diagnostic imaging allowed a judgment of partial response. Although a ratio of liver tumor volume to liver volume was 57% on admission of this patient, the ratio was reduced to 16% by the 14th course of 5-FU hepatic arterial infusion immediately before the catheter was occluded. The ratio was 18% after the 7th course of IRIS therapy, and the diagnostic imaging showed a partial response. Hepatic arterial infusion therapy is one of the treatment methods characterized by a lower incidence of adverse reactions, relatively low cost, and expectation of high anti-tumor efficacy as compared to chemotherapy such as FOLFIRI. IRIS therapy does not require a port insertion and it costs about a half of FOLFIRI therapy. When used as a second-line therapy for unresectable colorectal cancer, IRIS therapy has demonstrated non-inferiority compared to FOLFIRI in a phase III clinica (l FIRIS) study.
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PMID:[A case of unresectable multiple hepatic metastases from colorectal cancer successfully treated with IRIS (S-1, CPT-11) therapy]. 2122 44

A 37-year-old female, who had undergone a low anterior resection for lower rectal cancer, had been received chemotherapy (FOLFOX4, FOLFIRI) for 2 years because of right ovarian metastasis occurred and removed 9 months after the first operation. One month after 2 years of continued chemotherapy, progressive metastases happened to occur successively (rt lunge, left ovarium, liver, para-aortic lymphonode, Virchow lymphonode and bone). Right upper lobe pnemonectomy was performed first, then, peritonectomy, total hysterectomy with left oophorectomy and a partial resection of the small bowel were done. IRIS, as postoperative chemotherapy, performed with hepatic arterial infusion (HAI) of CPT-11 and 5- FU resulted in getting a minimal response for about 10 months. Because of the hepatic arterial thrombosis at 10 months after the previous operation, we could not continue HAI with systemic chemotherapy, that was resulted in the progresion of mutiple metastases, and that the patient died 62 months after the first surgery. Immunohistochemical analyses with MIB-1 stainning of four surgical specimens revealed 80% positive cells in the cancerous tissues.
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PMID:[A case of the long-term survivor of rectal cancer who suffered from successive metastases to ovarium, peritoneum, liver, bone and para-aortic lymphonode]. 2220 41

In a patient with multiple liver metastases of colorectal cancer in whom tumor response had been achieved by 5-FU hepatic arterial infusion, the catheter for arterial infusion chemotherapy was occluded resulting in re-elevation of tumor marker levels. Second-line IRIS therapy using S-1 and CPT-11 was started. IRIS therapy reduced tumor marker levels to a degree greater than that previously achieved with 5-FU hepatic arterial infusion, and diagnostic imaging allowed a judgment of partial response. But tumor marker levels increased gradually. After all, diagnostic imaging allowed a judgment of progressive disease and an eminent elevation of tumor marker levels in one year. Third-line panitumumab therapy was started. Panitumumab therapy reduced tumor marker levels to a degree greater than that previously achieved with 5-FU hepatic arterial infusion and IRIS therapy, and diagnostic imaging allowed a judgment of partial response. We report herein a successful case. Hepatic arterial infusion therapy is one of the treatment methods characterized by a lower incidence of adverse reactions, relatively low cost, and expectation of high anti-tumor efficacy as compared to chemotherapy such as FOLFIRI. IRIS therapy does not require a port insertion and pump carrying, and its cost is about half of FOLFIRI therapy. When used as second-line therapy for unresectable colorectal cancer, non-inferiority of IRIS therapy to FOLFIRI therapy has been demonstrated in a phase II/III clinica (l FIRIS) study. We may say that IRIS therapy is promising as an equivalent to hepatic arterial infusion therapy in the treatment of liver metastases of colorectal cancer. In addition, we may say that panitumumab therapy is promising as an equivalent to hepatic arterial infusion therapy and IRIS therapy.
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PMID:[A case of unresectable multiple hepatic metastases from colorectal cancer successfully treated with panitumumab therapy on third-line]. 2220 44

A 66-year-old woman underwent total pelvic exenteration for a pelvic tumor. The pathological diagnosis was sigmoid colon cancer T4b(in the small intestine, uterus, and vagina), N0, M0, Stage II . The patient was treated with XELOX for 6 months as adjuvant chemotherapy and was then treated with IRIS for another 6 months. Brain metastasis developed in the left occipital lobe after 12 months, and she underwent craniotomy and enucleation of the tumor. Liver metastasis and peritoneal dissemination metastasis developed 16 months after her initial diagnosis. The patient underwent re-craniotomy and radiotherapy for recurrence of the brain metastasis 18 months after diagnosis and started taking TAS-102 3 months later. She began treatment with CPT-11 plus panitumumab 24 months after diagnosis, and the dose was increased 9 months later(ie, 35 months after the initial diagnosis). The patient remains alive 42 months after surgery.
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PMID:[Long-Term Survival of a Patient with Sigmoid Colon Cancer with Multiple Visceral Metastases]. 2813 49

The patient was 55-year-old woman, undergoing Hartmann operation by the sigmoid colon diverticulum perforation, 2 years later visited our hospital with abdominal pain. Although lower endoscopy and histological examination could not be performed due to stoma stenosis, we diagnosed cecal carcinoma, liver metastasis, distant lymph node metastasis from CT and PET-CT, CapeOX plus Bmabtherapy and IRIS plus Bmabtherapy were performed. After that, repeated intestinal obstruction due to exacerbated stoma stenosis, metastatic lesion increased in CT examination, furthermore the patient had hope of stoma closure, we decided to resect the primacy tumor, performed subtotal colonectomy and stoma closure. Pathological diagnosis revealed RAS wild type. After surgery, Pmabplus CPT-11 therapy was performed and the metastatic lesion was temporarily shrunk but re-exacerbated, the patient died 2 years 2 months after the first treatment started, 7 months after the primary tumor resection. In the treatment of colorectal cancer, when metastatic lesion is unresectable, chemotherapy is often carried out except when the primary tumor is symptomatic. In our case, although the primary tumor was asymptomatic, an intestinal obstruction due to stoma stenosis was developed and it was necessary to examine whether to use anti-EGFR antibody drugs, therefore we performed operation.
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PMID:[A Case of Surgery after Chemotherapy for Cecal Cancer with Onset of the Stenosis of the Colostomy]. 2948 45