Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimetastatic effect of a new water-soluble derivative of camptothecin, 7-ethyl-10-(4-(1-piperidino)-1-piperidino) carbonyloxy-camptothecin (CPT-11), were examined in several metastatic murine tumor systems. Intravenous (i.v.) injection of CPT-11 into BALB/c mice inhibited lung metastasis by i.v. inoculated, metastatic colonic adenocarcinoma 26 (C26) cells, C26NL-17, in BALB/c mice. This treatment was also effective in C57BL/6 mice against lung metastasis by i.v. inoculated B16-F10 and B16-BL6 cells, highly metastatic variants of the B16 melanoma. Furthermore, intraperitoneal (i.p.) injection of CPT-11 significantly inhibited the growth of C26NL-22 cells, a highly metastatic variant of C26, inoculated subcutaneously (s.c.) into the left front footpads of BALB/c mice. Also, i.p. or i.v. injection of CPT-11 effectively inhibited the growth of 3LL tumors inoculated s.c. into the hind footpads of C57BL/6 mice. Moreover, following s.c. inoculation of either C26NL-22 or 3LL cells, combined surgical excision of the primary tumor and either i.p. or i.v. CPT-11 injections given before or after surgery markedly inhibited the formation of pulmonary metastases. These results show that a new derivative of camptothecin, CPT-11, has a potent inhibitory effect against both spontaneous and experimental lung metastasis.
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PMID:Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice. 337 Jul 38

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

It has been hypothesized that intratumoral thymidylate synthase (TS) gene expression might be used to select therapy for patients with disseminated colorectal cancer. We recently reported the results of a clinical trial in 46 patients with disseminated or recurrent colorectal cancer testing whether expression of TS within the primary tumor, as assessed by quantitative polymerase chain reaction (PCR) methodology, would predict the responsiveness of that cancer of fluoropyrimidine-based therapy. This trial demonstrated that intratumoral TS/beta-actin messenger RNA (mRNA) ratio can accurately predict which metastatic colorectal tumors will be resistant to a leucovorin-modulated 5-FU infusion and which have a high likelihood of responding to such a regimen. Results of other studies of adjuvant therapy in gastric cancer and colorectal cancer also indicated that TS expression within the tumor is predictive of response of 5-FU-based therapy. It may be possible to use this parameter prospectively to decide which patients should receive fluorinated pyrimidine therapy: Patients whose tumors express low TS levels would be likely to benefit from such therapy, whereas limited preliminary data suggest that patients whose tumors express high TS levels may benefit from irinotecan (CPT-11[Camptosar]).
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PMID:Thymidylate synthase as a predictor of response. 972 90

Three active antitumor agents, i.e. 5-fluorouracil (5-FU), oxaliplatin and CPT-11, are available for the treatment of advanced colorectal cancer (CRC) patients and have been successfully combined in two-drug regimens. Hence, CRC has become a chemosensitive disease, but the optimal combination of these agents in first-line treatment remains to be determined. We report the first case of the combination of CPT-11 with oxaliplatin, 5-FU and folinic acid (FA) as first-line chemotherapy for a patient with a pre-occlusive sigmoid adenocarcinoma and synchronous bulky liver metastases. CPT-11 was given at 125 mg/m2, prior to the start of a chronomodulated 4-day infusion of oxaliplatin 25 mg/m2/day, 5-FU 800 mg/m2/day and FA 300 mg/m2/day repeated every 2 weeks. The doses could be escalated to 150 mg/m2 for CPT-11 and 900 mg/m2/day for 5-FU. After six cycles of chemotherapy 70% reduction in tumor size was documented in the liver. The primary tumor was no longer detectable by barium enema. The toxicity included three episodes of grade 4 neutropenic fever, and two episodes of severe diarrhea and vomiting with dehydration. A cumulative grade 2 neurosensory toxicity was observed after six cycles. Following surgery of the primary tumor, because of the major hepatic tumor response and of the absence of extra-hepatic metastases, the patient might be registered for a liver transplantation program. This first report of combining the three active agents in CRC every 2 weeks led to a high dose intensity of each agent and was associated with a dramatic tumor response of a very advanced disease in a patient with already altered performance status. The antitumor activity in this patient suggests that a three-drug intensified regimen might be feasible and active. A prospective study appears warranted to further examine the efficacy and toxicity of this therapeutic approach, and to determine whether it may increase the fraction of advanced CRC patients becoming resectable. This aggressive chemotherapy program may contribute to a re-examination of the usefulness of liver transplantation in patients with metastatic CRC confined to the liver.
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PMID:Dramatic tumor response of bulky liver metastases following treatment with CPT-11 and a chronomodulated 4-day infusion of 5-fluorouracil, folinic acid and oxaliplatin every 2 weeks in a colorectal cancer patient. 1089 41

Tumor cells that contaminate hematopoietic cell preparations contribute to the relapse of neuroblastoma patients who receive autologous stem cell rescue as a component of therapy. Therefore, effective purging methods are needed. This study details in vitro experiments to develop a viral-directed enzyme prodrug purging method that specifically targets neuroblastoma cells. The approach uses an adenovirus to deliver the cDNA encoding a rabbit liver carboxylesterase that efficiently activates the prodrug irinotecan,7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11). The data show that an adenoviral multiplicity of infection of 50 transduces 100% of cultured neuroblastoma cells and primary tumor cells, irrespective of the level of tumor cell line contamination. Exposure of neuroblastoma cell lines or of mixtures of these cell lines with CD34(+) cells at a ratio of 10:90 to replication-deficient AdRSVrCE for 24 h and subsequent exposure of cells to 1-5 microM CPT-11 for 4 h increased the toxicity of CPT-11 to three neuroblastoma cell lines (SJNB-1, NB-1691, and SK-N-SH) from approximately 20-50-fold and eradicated their clonogenic potential. Also, after "purging," RNA for neuroblastoma cell markers (tyrosine hydroxylase, synaptophysin, and N-MYC) was undetectable by reverse transcription-PCR. In contrast, the purging protocol did not affect the number or type of colonies formed by CD34(+) cells in an in vitro progenitor cell assay. No bystander effect on CD34(+) cells was observed. The method described is being investigated for its potential clinical utility, particularly its efficacy for use with patients having relatively high tumor burdens, because no published methods have been shown to be efficacious when the tumor burden exceeds 1%.
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PMID:A virus-directed enzyme prodrug therapy approach to purging neuroblastoma cells from hematopoietic cells using adenovirus encoding rabbit carboxylesterase and CPT-11. 1143 45

We determined the antitumor and antimetastatic efficacy of the camptothecin analogue DX-8951f in an orthotopic metastatic mouse model of pancreatic cancer. DX-8951f showed efficacy against two human pancreatic tumor cell lines in this model. These cell lines were transduced with the green fluorescent protein, enabling high-resolution visualization of tumor and metastatic growth in vivo. The DX-8951f studies included both an early and advanced cancer model. In the early model, using the human pancreatic cancer lines MIA-PaCa-2 and BxPC-3, treatment began when the orthotopic primary tumor was approximately 7 mm in diameter. DX-8951f was significantly effective against both MIA-PaCa-2 and BxPC-3. In contrast, 2', 2'-difluorodeoxycytidine (gemcitabine), the standard treatment for pancreatic cancer, did not have significant efficacy against MIA-PaCa-2. Although gemcitabine showed significant activity against BxPC-3 primary tumor growth, it was not effective on metastasis. In the model of advanced disease, using BxPC-3, treatment started when the orthotopic primary tumor was 13 mm in diameter. DX-8951f was significantly effective in a dose-response manner on the BxPC-3 primary tumor. DX-8951f also demonstrated antimetastatic activity in the late-stage model, significantly reducing the incidence of lymph node metastasis while eliminating lung metastasis. In contrast, gemcitabine was only moderately effective against the primary tumor and ineffective against metastasis at both sites in the late-stage model. Therefore, DX-8951f was highly effective against primary and metastatic growth in this very difficult-to-treat disease and showed significantly higher efficacy than gemcitabine, the standard treatment of pancreatic cancer. DX-8951f, therefore, has important clinical promise and has more positive features than the currently used camptothecin analogue CPT-11, which requires metabolic activation and is toxic.
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PMID:Efficacy of camptothecin analog DX-8951f (Exatecan Mesylate) on human pancreatic cancer in an orthotopic metastatic model. 1251 81

Paraneoplastic neurosyndrome (PNS) is a group of neurological disorders caused by or associated with neoplasms that are not direct effects of the primary tumor or of a metastasis to the involved organs. Chemotherapy, radiotherapy, immunosuppressive therapy, and plasmapheresis have been performed to treat PNS, but improvement of the neurological disorder is rather rare. A 64-year-old man was referred to our hospital with dysesthesia of the extremities and ataxic gait. Small cell lung cancer was diagnosed in another hospital and chemotherapy (CDDP 80 mg/m2 + VP-16 100 mg/m2) was performed. A partial response was obtained with this treatment, but the neurological dysfunction was exacerbated. Three months later, the patient was admitted to our hospital. On treatment with CDDP 80 mg/m2 (day 1) and CPT-11 80 mg/m2 (days 1, 8 and 15) and subsequent radiation therapy (60 Gy), his neurological disorder improved. We consider that neurological symptoms are important signs of malignancy in PNS and that a full course of treatment could improve the neurological disorders.
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PMID:[A case of paraneoplastic syndrome improved following chemoradiotherapy for lung cancer]. 1277 4

Cancer patients undergoing triple therapy (CPT-11, 5-fluorouracil, and leucovorin) often present with severe delayed diarrhea as a result of chemotherapy-induced gastrointestinal (GI) toxicity and inflammation. RDP58 is a novel, anti-inflammatory, D-amino acid decapeptide that inhibits the production of tumor necrosis factor alpha, IFN-gamma, and interleukin 12, and has been shown to effectively inhibit clinical symptoms and intestinal inflammation in several rodent models of chemically induced colitis, nonhuman primates with spontaneous colitis, and humans with mild to moderate ulcerative colitis. We evaluated RDP58 as a potential protective agent in chemotherapy-induced GI inflammation. Oral administration of RDP58 significantly decreased the incidence of diarrhea and improved the survival rates of mice treated with toxic doses of CPT-11 or 5-fluorouracil. Histological analysis showed that RDP58 significantly reduced the destruction of the intestinal mucosa by inhibiting local overproduction of tumor necrosis factor alpha, IFN-gamma, and interleukin 12 in vivo. Furthermore, RDP58 administration allowed the maximum tolerated dose of CPT-11 to be doubled in tumor-bearing mice resulting in significantly enhanced primary tumor responses and prolongation of time to relapse without a concomitant increase in GI toxicity. Our results suggest that RDP58 may have clinical utility in cancer therapy by preventing treatment-associated GI toxicity and potentially increasing the effectiveness of chemotherapy.
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PMID:Oral RDP58 allows CPT-11 dose intensification for enhanced tumor response by decreasing gastrointestinal toxicity. 1510 94

We report a case of advanced rectal cancer successfully treated with a combination of S-1 and CPT-11 as neoadjuvant chemotherapy. The patient, a 61-year-old man, had a rectal cancer with pelvic viscera invasion and severe stenosis. After colostomy for removing stenosis, he was treated with a combination of S-1 and CPT-11 (S-1 120 mg/body day on day 1-14, CPT-11 120 mg/body/day on day 1 and day 15, every 4 weeks). Seven courses of treatment resulted in a marked reduction of the primary tumor and disappearance of invasion. Subsequently, rectal amputation for curative intent was done. No surgical complication was observed. On microscopic examination, only a few tumor cells were detected in the granulation tissue of the resected rectum and no tumor cells in dissected LNs. This case demonstrates the effectiveness and safety in a neoadjuvant setting of a combination of S-1 and irinotecan for rectal cancer.
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PMID:[Neoadjuvant chemotherapy with combination of S-1 and CPT-11 in advanced rectal cancer - a case report]. 1794 Mar 87


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