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

A Phase II study of CPT-11, a new camptothecin, was performed in patients with primary lung cancer. Patients with previously untreated non-small cell carcinomas (group A), or previously treated non-small cell carcinomas (group B), and with small cell carcinomas (group C), were enrolled in this study. CPT-11 was given at a dose of 100 mg/m2 i.v. infusion once a week for three weeks or more. Out of 153 patients enrolled, 128 (A: 67; B: 26; C: 35) were assessed to be evaluable for response by an extramural review committee. Response rates were 34.3% (23/67) for A, 0% (0/26) for B and 37.1% (13/35) for C. The response rate was 50% for previously untreated patients (4/8), and 33.3% for previously treated patients (9/27) including 2 complete responses in the group C. Major toxicities were leukopenia, nausea/vomiting, diarrhea, anorexia and alopecia. Leukopenia and diarrhea were considered to be dose limiting toxicities, but they were reversible. It was, however, suggested that some patients should be monitored carefully for severe reactions and delay in recovery. The results showed that CPT-11 was highly effective against non-small cell and small cell carcinomas of the lung.
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PMID:[A phase II study of CPT-11, a camptothecin derivative, in patients with primary lung cancer. CPT-11 Cooperative Study Group]. 185 8

A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4-34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer.
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PMID:[A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers]. 187 24

An early Phase II study of CTP-11, a new derivative of Camptothecin, in gynecologic cancers was carried out by a cooperative study group of 9 institutions. Forty-six patients were enrolled, and there were 14 cases of ovarian cancers, 7 of cervical cancer, 6 of uterine body cancers and 1 of endometrial stromal sarcoma which satisfied study criteria. The response rate in ovarian cancers was 21.4%, and in cervical cancers 42.9%, among an overall rate of 21.4%. Three out of 6 patients with objective response had undergone previous chemotherapies including cisplatin, suggesting that CPT-11 was effective for patients with no response or refractory to these therapies. Leukopenia was a major adverse reaction with an incidence of 60.0% (grade 2 or more). Gastrointestinal symptoms such as nausea vomiting, anorexia and diarrhea were frequently observed (grade 2 or more; 13.3-43.3%). These were generally tolerable except in a few cases. Besides these reactions, alopecia was also observed (33.3%), but severe adverse reactions such as nephropathy were not. These results suggested that CPT-11 was effective against ovarian cancer and cervical cancer. The recommended dose regimen for a late phase II study is considered to be 100 mg/m2 once weekly and 150 mg/m2 once every 2 weeks.
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PMID:[An early phase II study of CPT-11 in gynecologic cancers. Research Group of CPT-11 in Gynecologic Cancers]. 201

In clinical use, irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea. We investigated whether baicalin, an inhibitor of beta-glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT-11, SN-38 (7-ethyl-10-hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT-11-induced intestinal toxicity in rats. CPT-11 (60 mg/kg i.v. once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium. Treatment with baicalin (25 mg/kg p.o. twice daily) or Kampo medicines (TJ-14 and TJ-114; 1 g/kg p.o. twice daily) from the day before to 4 or 10 days after the start of CPT-11 administration resulted in significantly decreased weight loss, improved anorexia and delayed onset of diarrheal symptoms. Histological examination revealed that Kampo medicine-treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats. These results suggest that the prophylactic use of Kampo medicines (TJ-14 and TJ-114) may be of value against CPT-11-induced intestinal toxicity.
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PMID:Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats. 749 18

The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. This article reviews the accumulated results of clinical and laboratory studies performed with these agents at The Johns Hopkins Oncology Center. In a phase I clinical and pharmacology trial of topotecan given as a 30-min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The daily x5 schedule has been developed further with dose escalation using granulocyte-colony-stimulating factor support in patients who have kidney or liver dysfunction and given in combination with cisplatin. In addition, a phase I trial of topotecan given as a 5-day continuous intravenous infusion to patients with refractory leukemia has had promising antileukemic responses. A separate series of in vitro studies indicates that a modest degree of resistance to the cytotoxicity of topotecan can be mediated by P-glycoprotein. A phase I and pharmacology study of irinotecan given as a 90-min infusion every 3 weeks has defined an MTD of 240 mg/m2, with dose escalation being limited by several toxicities. These included an acute treatment-related syndrome of flushing, warmth, nausea, vomiting, and diarrhea; a subacute combination of nausea, diarrhea, anorexia, and weight loss; and/or neutropenia. Antitumor activity has been observed with topotecan and irinotecan in patients with a variety of solid tumors and refractory leukemia in our studies, which supports the widespread enthusiasm for this group of compounds.
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PMID:Camptothecin analogues: studies from the Johns Hopkins Oncology Center. 752 Aug 44

A 62-year-old man was hospitalized in March 1990 due to upper abdominal discomfort and anorexia. The chest X-ray revealed an upper anterior mediastinal tumor, and abdominal ultrasound showed lymphadenopathy. Endoscopic examination of the stomach revealed a large, irregular ulcer, which was histologically confirmed to be malignant lymphoma by biopsy. Serum anti-HTLV-1 antibody was positive. A diagnosis of ATLL (lymphoma type) was made. The usual therapy for this disease, including the LSG4 and RCM protocols, was only transiently effective. Therefore, the patient was treated with CPT-11 (40 mg/m2) by intravenous infusion on 3 consecutive days with weekly repetition in November 1990. Complete remission was obtained after 2 weeks of treatment, and was maintained for 5 months. This case suggests that CPT-11 may be effective for the treatment of ATL.
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PMID:[Successful treatment of chemotherapy-resistant adult T cell leukemia/lymphoma by irinotecan hydrochloride (CPT-11)]. 813 1

A late phase II study of CPT-11 for advanced breast cancer was conducted at 27 institutions. Seventy-nine patients were enrolled, 75 were eligible for the study, and 65 were evaluable for efficacy. One complete response and 14 partial responses were obtained, and the response rate was 23%. The response rate of patients with prior endocrine therapy and prior chemotherapy including adriamycin or other anthracycline drugs was 27% (11/41) and 26% (12/46), respectively. The response rate for patients with estrogen receptor-negative tumors and premenopausal patients was 32% (6/19) and 27% (4/15), respectively. Responses were observed not only for soft tissue lesions such as lymph nodes (5/17), but also for distant metastases in the lungs (8/28) and bone (1/18). The major adverse reactions were myelosuppression and gastrointestinal symptoms. The incidence of Grade 2 or higher leukopenia, anemia, nausea/vomiting, anorexia, diarrhea and alopecia was 68%, 31%, 67%, 59%, 37%, and 30%, respectively. These results suggested that CPT-11 was a promising drug for advanced breast cancer.
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PMID:[A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer]. 821 Feb 51

A multi-institutional collaborative late phase II study of irinotecan hydrochloride (CPT-11) was performed on patients with advanced gastric cancer. CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion or as 150 mg/m2 fortnightly. Of 81 registered patients, 77 cases were eligible and 60 cases were evaluable for response. The overall response rate for evaluable cases was 23.3% (14/60), and the response rate was 16.1% (9/45) for the patients who had received prior chemotherapy. The primary tumor showed a 4.5% response, while metastatic lesions in the lymph-nodes, lungs, and liver showed response rates of 36.4%, 33.3%, and 17.4%, respectively. The major toxicities (> or = Grade 3) were leukopenia (41.2%), anemia (28.9%), diarrhea (22.4%) and anorexia (19.7%). These toxicities were generally reversible. CPT-11 showed activity against advanced gastric cancer, suggesting that further clinical studies of CPT-11 combined with other active chemotherapy agents are warranted.
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PMID:[Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group]. 821 Feb 54

A late phase II study of CPT-11 was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with advanced pancreatic cancer as a cooperative study of 19 institutions. From February 1990 to June 1992, 61 patients with advanced pancreatic cancer were enrolled in this study. Fifty-seven patients were evaluable for toxicity and 35 for response. CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion (regimen A) or as a 150 mg/m2 every two weeks (regimen B). The response rate was 11.4% (4/35). The primary tumor showed a 10.3% (3/29) response and the liver metastases showed a 10.5% (2/19) response. The major toxicities were myelosuppression and gastrointestinal symptoms. The incidences (> or = Grade 2) of leukopenia, anemia, anorexia, nausea/vomiting, alopecia and diarrhea were 61.4% (35/57), 56.1% (32/57), 70.2% (40/57), 56.1% (32/57), 40.4% (23/57) and 36.8% (21/57), respectively. The incidence of diarrhea was higher with regimen A than with regimen B, but the antitumor activity was no different between the two regimens. These results suggested that CPT-11 has some antitumor activity against advanced pancreatic cancer.
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PMID:[A late phase II study of CPT-11, irinotecan hydrochloride, in patients with advanced pancreatic cancer. CPT-11 Study Group on Gastrointestinal Cancer]. 821 Feb 55

A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT-11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma.
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PMID:[Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies]. 821 Feb 56


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