Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine platinum analogs are currently in clinical development, including three that contain the diaminocyclohexane substituent and five that contain the cyclobutanedicarboxylato leaving group. Many of them have shown activity in at least one cisplatin (CDDP)-resistant cell line, most commonly L1210 murine leukemia. In addition, most were less nephrotoxic than CDDP in preclinical evaluations. While these agents share certain key structural similarities, there are important differences in their toxicity profiles that may be exploitable in future combination therapies. Though neuropathy has been a troubling toxicity with two of the three diaminocyclohexane (DACH) compounds, it differs in that it appears to be less chronic and cumulative with oxaliplatin (I-OHP), which is also associated with much less myelosuppression. Of the cyclobutanedicarboxylato compounds that are structurally related to carboplatin (CBDCA), there are several notable differences. For several compounds, isolated neutropenia has been dose-limiting and thrombocytopenia, which is common with CBDCA, has been uncommon. Like CBDCA, neurotoxicity has not been an issue with this group. Therefore, the potential for dose escalation with a colony stimulating factor (CSF) appears enhanced. Furthermore, promising early clinical leads, such as the substantial response rates in cervix and head and neck cancers with 254-S and in patients with colon cancer using circadian modulation of I-OHP, require careful evaluation. Preclinical synergy data are also cited that suggest other potential clinical leads. The development of a number of these agents has been complicated by unanticipated issues, including unexpected chronic dose-limiting neurotoxicity with ormaplatin (OP), formulation and stability problems with liposomal-neodecanoato-diaminocyclohexane platinum (II) (L-NDDP), and problematic nephrotoxicity with zeniplatin (ZP). However, several of these new compounds are likely to enter broader phase II and III development and should provide important information not only about the utility of the agents themselves but also about the predictive value of some of these preclinical models of CDDP resistance.
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PMID:The current status of new platinum analogs. 146 69

Recurrence of gastric cancer or colon cancer was observed in some patients who received 5-fluorouracil (5-FU) high-dose continuous Methotrexate (MTX)-Leucovorin (LV) therapy (FML therapy) previously. 5-FU high-dose 48-hours continuous therapy (5-FU therapy) as maintenance therapy for the patients was performed in the hospital and successively at home. The patients included 3 with recurrent gastric cancer and 2 with recurrent colon cancer: there were 4 males and 1 female, the mean age was 51.8 years (33-59 years). All patients had received FML therapy during the hospital stay before the maintenance chemotherapy at home. 5-FU therapy (30 mg/kg/day x 2 days/w), 30.2 courses on an average (11-40 courses), was performed through a catheter (Port-A-Cath), which was introduced into the right subclavian vein and placed under the skin, with a Baxter infusion pump. The concentration of 5-FU was 197 +/- 172-401 +/- 127 ng/ml between the 2nd and 48th hour. Adverse reaction included anorexia in 5 patients, stomatitis in 4, pigmentation in 4, leukopenia in 3, neuropathy in 2 and alopecia in 1. The therapy was effective for 10.4 months on an average (4-18 months) and the mean survival period was 12.0 months (7-18 months).
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PMID:[Usefulness of 5-FU high-dose continuous therapy at home in patients with recurrent gastric and colon cancer]. 780 45

Liver transplantation is complicated by specific medical problems. Diabetes mellitus occurs in 4-20% of patients undergoing liver transplantation. Patients with primary sclerosing cholangitis and ulcerative colitis experience up to a 13% incidence of colon cancer after transplantation. Lymphomas occur in 1-3% of patients after transplantation and account for 57% of malignancies occurring in adult patients. Atraumatic bone fractures occur in 22-38% of patients and neurological complications, including seizures, headache, and neuropathy occur in 19-47% of patients following liver transplantation. Patients undergoing liver transplantation may experience recurrence of their primary liver disease: hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, or primary sclerosing cholangitis. In patients not receiving immunoprophylaxis after transplantation for chronic hepatitis B, recurrent hepatitis B is seen in up to 90% of patients. This can be markedly reduced with hyperimmune globulin immunoprophylaxis. Recurrent hepatitis C is seen in the majority of patients; current treatment modalities are inadequate. Recurrence of primary biliary cirrhosis or primary sclerosing cholangitis in the allograft is infrequent. Autoimmune hepatitis may recur in up to 26% of patients following liver transplantation. Primary disease recurrence in the allograft and preventive strategies are discussed.
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PMID:Medical problems occurring after orthotopic liver transplantation. 928 32

Oxaliplatin is a new platinum analog of the DACH family. Recent preclinical data have confirmed its non overlapping spectrum of activity with cisplatin, including acquired and intrinsic platinum resistant cell lines (as KB-CP, A 2780, HT29, CaCo2 colon cancer). When combined with other cytotoxic agents (5FU, SN38, CDDP, carboplatin), oxaliplatin has additive and/or synergistic antitumoral effects on various in vitro and in vivo models (colon, breast, ovarian and epidermoid tumors). Phase II trials have confirmed a sensorial peripherical neuropathy as its limiting toxicity while neither ototoxicity nor renal toxicities and only limited myelotoxicity were noted. Available phase II studies have established its antitumoral activity as single agent in 5FU refractory colon carcinoma while preliminary results suggest efficacy in cisplatin resistant ovarian cancer, in non small cell lung cancer, non Hodgkin lymphoma. Antitumoral activity has been observed during phases 1 in melanoma, glioma, breast and oesophageal cancers. A high response rate (28-65%) with the triple association (FU/folinic acid/oxaliplatin) has been reported in advanced colon cancer treated in first and second line settings. The results of two randomized phase III studies (FU/folinic acid +/- oxaliplatin) are expected. The oxaliplatin/cisplatin combination as salvage regimen had produced significant antitumoral activity (response rate: 45%) in resistant/refractory ovarian cancer. Finally, recent experimental and clinical data have outlined the potential interest in the development of this new original platinum compound. New single agent phases II are expected in other tumor types as well as new oxaliplatin combinations are ongoing (phase I trials of oxaliplatin/CPT-11 and of oxaliplatin/carboplatin, phase II study of oxaliplatin-vinorelbine in lung cancer.
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PMID:[Oxaliplatin: the first DACH platinum in clinical practice]. 929 71

Neutropenia is the dose-limiting toxicity of docetaxel in children. This Phase I trial was designed to determine the maximum tolerated dose, the dose-limiting toxicities, and the incidence and severity of other toxicities of docetaxel with filgrastim (G-CSF) support in children with refractory solid tumors. Docetaxel was administered as an i.v. infusion for 1 h every 21 days with a starting dose of 150 mg/m2 and an escalation to 185 mg/m2 and 235 mg/m2 in subsequent patient cohorts. G-CSF (5 microg/kg/day) was administered s.c., starting 48 h after docetaxel and continuing until the post-nadir neutrophil count reached 10,000/microl. Seventeen patients received 27 courses of docetaxel with G-CSF support. Generalized erythematous desquamating skin rash and myalgias were dose-limiting at 235 mg/m2. Localized and generalized rashes were seen at all of the three dose levels. Neutropenia (median nadir, 95/1microl) occurred at all of the dose levels but was brief in duration and not dose-limiting. Thrombocytopenia was minimal (median platelet count nadir, 139,000/microl), and the severity of neutropenia and thrombocytopenia did not seem to be related to the docetaxel dose. Other docetaxel-related toxicities included hemorrhage (associated with mucositis), sepsis, hypersensitivity reaction, transient elevation of liver enzymes, stomatitis, back pain, asthenia, and neuropathy. One minor response was observed in a patient with colon cancer. The maximum tolerated dose of docetaxel with G-CSF support in children is 185 mg/m2, which is 50% higher than the maximum tolerated dose of docetaxel alone in children and 85 % higher than the recommended adult dose.
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PMID:Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: a collaborative Pediatric Oncology Branch, National Cancer Institute and Children's Cancer Group trial. 1021 6

Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3-4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85 mg/m(2)) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200 mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2-4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2-4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.
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PMID:N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. 1645 89

We reported a case of sigmoid colon cancer with left supraclavicular lymph node involvement that completely responded to FOLFOX4 therapy following laparoscopy-assisted colectomy (LAC). A 69-year-old female presented with left supraclavicular tumor and was diagnosed as sigmoid colon cancer. Abnormally high CEA (128 ng/mL) and CA19-9 (59.3 U/mL) levels were detected in serum. She was operated palliatively by LAC, and FOLFOX4 therapy was initiated. The serum CEA and CA19-9 values regained their normal level after 5 and 4 courses of FOLFOX4, respectively. After 5 courses, metastatic nodes disappeared on her CT. After 12 courses no abnormal accumulations were detected on FDG-PET. Antitumor efficacy was judged as CR. Grade 1 neutropenia and grade 2 peripheral neuropathy were noted, but no other serious adverse reactions occurred during FOLFOX4 therapy. CR has been maintained at present. She has been treated with FOLFOX4 therapy without oxaliplatin to prevent neuropathy. Establishment of maintenance therapy following CR to FOLFOX4 is awaited.
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PMID:[A case of complete response in supraclavicular lymph node involvement from cancer of the sigmoid colon to FOLFOX4 therapy after laparoscopy-assisted colectomy]. 1840 42

Patients with colorectal cancer present a number of supportive care challenges including those related to the underlying disease, such as gastrointestinal obstruction, nausea, anorexia, and fatigue, and those caused by the treatments, such as oral mucositis, neuropathy, and chemotherapy-induced diarrhea. Unique toxicities can accompany specific routes of administration of colon cancer drugs such as hand-foot syndrome with oral capecitabine and continuous infusion fluorouracil and biliary sclerosis with intrahepatic arterial floxuridine. The newer targeted therapies also present new toxicities, such as cardiovascular events and wound-healing complications with bevacizumab and rash and hypomagnesemia with cetuximab. Recent additions to the therapeutic armamentarium have presented new challenges, such as oxaliplatin-induced peripheral neuropathy, capecitabine-induced hand-foot syndrome, cetuximab-induced rash, and bevacizumab-associated arterial thrombotic events, bowel perforation, hypertension, and wound-healing complications. This article focuses on the prevention and management of several of these more common symptoms and toxicities.
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PMID:Supportive care in the management of colon cancer. 1863 90

A 62-year-old woman complained of thin feces, lower blood and abdominal pain, and she was diagnosed as having bowel obstruction due to sigmoid colon cancer. Abdominal CT showed peritoneal dissemination and ascites on the surface of liver. The serum CEA levels were 663.7 ng/mL. We established a diagnosis of unresectable sigmoid colon cancer accompanied by severe peritoneal dissemination and therefore performed only transverse colostomy in April, 2006. Pathological examination of omental dissemination demonstrated moderately-differentiated adenocarcinoma. FOLFOX4 therapy was started on April, 2006. Primary lesion decrease and release from bowel obstruction after 4 cycles was judged as a partial response. The partial response continued, and the serum CEA decreased 18.5 ng/mL after completion of 16 cycles, but grade 3 neuropathy occurred. We started S-1 as second-line chemotherapy in May, 2007. There was primary lesion re-growth after 4 cycles, so we changed to S-1+CPT-11 therapy. The adverse events were grade 3 neuropathy and leucopenia throughout the course. Chemotherapy is now continued on an outpatient basis, 24 months after the medical treatment started. FOLFOX4 therapy is useful for patients with advanced colon cancer accompanied by peritoneal dissemination.
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PMID:[A case of advanced sigmoid colon cancer with peritoneal dissemination responding to FOLFOX4 therapy]. 1909 17

The standard treatment for colon cancer is surgical excision. Adjuvant chemotherapy is intended to reduce the risk of relapse, which is responsible for the death of nearly half of all patients treated surgically for localised disease. After surgery for stage III disease (node involvement without metastases), the 5-year survival rate is about 63% with adjuvant chemotherapy combining fluorouracil and folinic acid, versus 51% with placebo, a statistically significant difference. After surgery for stage II disease (tumour spread beyond the intestinal wall but no node involvement), a meta-analysis updated in 2008 showed no impact of adjuvant chemotherapy on the overall survival rate. Fluorouracil + folinic acid administration according to the de Gramont protocol is the standard adjuvant treatment. The addition of regional fluorouracil chemotherapy did not further improve outcome in a trial in 1501 patients with stage II or stage III disease. The fluorouracil precursors, capecitabine and tegafur, provide no advantages in terms of efficacy or tolerability. These oral drugs have not been compared with the de Gramont protocol. A trial comparing raltitrexed versus fluorouracil + folinic acid was stopped because of an excess of deaths in the raltitrexed arm. In two large trials, each including more than 2000 patients, the addition of oxaliplatin to the fluorouracil + folinic acid combination (Folfox 4 protocol) in patients with stage III disease appeared to slightly improve overall survival in patients under 65 years of age, but severe neuropathy, diarrhoea, nausea and vomiting were more frequent. In three trials in a total of more than 3000 patients with stage III disease, the addition of irinotecan did not improve the efficacy of the fluorouracil + folinic acid combination, while serious adverse effects were more frequent. No new drugs intended for the treatment of colon cancer have been introduced since 2006, but better evaluation of existing drugs means that patients with stage III colorectal cancer can now be offered a choice between standard intravenous fluorouracil and oral capecitabine or tegafur. Oxaliplatin adjunction is another option for patients under 65. The adverse effect profile is an important factor in the choice of treatment.
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PMID:Adjuvant chemotherapy for localised colon cancer. Fluorouracil + folinic acid for node-positive, non-metastatic disease. 2148 94


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