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)

Colorectal cancers frequently overexpress the epidermal growth factor receptor. Gefitinib (Iressa), an inhibitor of the epidermal growth factor receptor tyrosine kinase, is synergistic with oxaliplatin in preclinical colon cancer models. The authors conducted a phase I/II trial of gefitinib plus oxaliplatin in patients with previously treated metastatic colorectal cancer. In the phase I portion, 14 patients received oxaliplatin 130 mg/m2 intravenously every 21 days and gefitinib orally daily at 1 of 2 dose levels: 250 mg/day (8 patients), and 500 mg/day (6 patients). There were no objective responses. Three patients (38%) in the 250-mg cohort experienced disease stabilization for a median of 12 weeks, and 1 patient in the 500-mg cohort had stable disease for 18 weeks. Nausea/vomiting and rash were dose limiting. The randomized phase II part of the trial, in which patients were to receive oxaliplatin with or without gefitinib, was canceled due to the inactivity of single-agent gefitinib observed in the phase I portion, and emergent phase III data regarding the minimal activity of single-agent oxaliplatin. The authors conclude that the combination of gefitinib plus oxaliplatin is inactive in advanced colorectal cancer.
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PMID:Phase I/II trial of gefitinib and oxaliplatin in patients with advanced colorectal cancer. 1606 74

Monoclonal antibodies against the epidermal growth factor receptor have proven efficacy as monotherapy and in combination with chemotherapy in patients with metastatic colorectal cancer (CRC: mCRC). Initial clinical trials in CRC used the human-murine chimeric monoclonal antibody cetuximab. Ongoing studies are being conducted to evaluate the efficacy and safety of the fully human anti-epiderman growth factor receptor monoclonal antibody panitumumab. The results of a phase III trial which compared panitumumab as a single agent to best supportive care in patients with previously treated metastatic CRC have recently been reported Pantitumumab therapy resulted in a 46% reduction in the risk of tumor progression and a partial response rate of 8%. Rash was reported in 90% of patients with increased severity significantly correlated with improved medium overall survival (OS). Further clinical studies re ongoing and planned to test panitumumab in combination with chemotherapy in first-line therapy of advanced-stage CRC and adjuvant treatment of colon cancer.
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PMID:Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. 1679 85

On September 27, 2006, the U.S. Food and Drug Administration granted approval to panitumumab (Vectibix, Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Panitumumab approval is based on the results of a single, open-label, randomized, multinational study that enrolled 463 patients with EGFR-expressing (at least 1+ membrane staining in > or =1% of tumor cells) metastatic colorectal cancer. Patients were randomized to either best supportive care (BSC) alone or BSC plus panitumumab, 6 mg/kg i.v., every other week. The primary study endpoint was progression-free survival (PFS), determined by an independent review committee that was blinded as to treatment assignment. BSC patients who progressed were eligible to receive panitumumab. The study patients' median age was 62 years, with 40% aged > or =65; 63% were male, 99% were white, 86% had a baseline Eastern Cooperative Oncology Group performance status score of 0 or 1, and 67% had colon cancer. The median time from diagnosis of metastases was approximately 19 months and the median number of prior therapies was 2.4. The PFS duration was significantly longer among patients randomized to receive panitumumab in addition to BSC (n = 231) compared with BSC alone (n = 232). The median and mean PFS times were 56 and 96.4 days, respectively, for patients receiving panitumumab and 51 and 59.7 days, respectively, for patients receiving BSC alone. Nineteen partial responses (8%, 95% confidence interval [CI], 5.3%-12.5%) were observed in panitumumab treated patients. The median duration of response was 17 weeks (95% CI, 16-25 weeks). Approximately 75% of patients in the BSC alone arm crossed over to receive panitumumab after disease progression. There was no difference in overall survival between the two study arms. The most common adverse events were skin rash, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea. The most serious adverse events were pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, diarrhea, and constipation.
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PMID:FDA drug approval summary: panitumumab (Vectibix). 1752 46

Dermatomyositis (DM) is an uncommon inflammatory myopathy with characteristic rash accompanying, or more often preceding, muscle weakness. There is a well-recognized association between DM and several cancers, such as ovarian cancer, breast cancer, melanoma, colon cancer, and non-Hodgkin lymphoma. We report the first case of cancer of unknown primary site associated with DM. A 62-yr-old woman presented to us with both shoulder painful swelling and facial edema. She was diagnosed previously as cancer of unknown primary site, histologically confirmed with squamous cell carcinoma in a pelvic mass. For the following days, she complained of erythematous face followed by progressive weakness of the proximal muscles of upper and lower limbs. The laboratory tests showed an increased muscle enzyme and acute phase reactants. The electromyogram showed the typical findings of DM. After the treatment with high dose steroid and methotrexate, the proximal motor weakness improved, and she received palliative radiation therapy.
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PMID:Dermatomyositis associated with cancer of unknown primary site. 1792 50

Bevacizumab is the fi rst vascular endothelial growth factor-targeted agent shown to increase survival in patients receiving first- and second-line intravenous 5-FU-based chemotherapy for the treatment of metastatic colorectal cancer. Bevacizumab is typically well tolerated and its major side effects include hypertension, proteinuria, bleeding, gastrointestinal perforation and arterial thrombotic events. Although exfoliative dermatitis has been described as a side effect in 19% of patients, skin rash (type unspecified) has rarely been described in patients following infusion of bevacizumab. We recently reported the fi rst patient with colon cancer manifesting a correlation between rash and a positive drug response with bevacizumab. A 49-year old male with T3 N1 M1 rectal carcinoma received modified FOLFOX-6/bevacizumab, which he tolerated very well except for grade 2 skin rash related to bevacizumab. The rash continued to progress as the serum carcinoembryonic antigen decreased significantly. Computed tomography and positron emission tomography scan confirmed response to FOLFOX/bevacizumab. We therefore believe that this rash was linked to bevacizumab administration and correlated with response to therapy. Grade 1/2 rash has been described in patients after infusion of bevacizumab in initial phase I and II studies. Skin rash was observed in 34% and 46% of patients in the Kabbinavar's study receiving 5 mg/kg dose and 10 mg/kg respectively but no patient developed > grade 3 rash. This toxicity was not well described in pivotal phase III studies. On the other hand, acneiform rash occurs in > 90% patients who receive cetuximab and panitumumab, severity of which appears to be predictive of response. To our knowledge, this case report is the second report of possible correlation between rash and a positive drug response associated with bevacizumab and warrants further investigation of similar observation.
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PMID:Correlation between rash and a positive drug response associated with bevacizumab in a patient with advanced colorectal cancer. 1850 Oct 75

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

Malignancy and interstitial lung disease (ILD) are 2 conditions associated with dermatomyositis (DM) that are responsible for a significant portion of the morbidity and mortality related to this disease; however, they rarely occur in the same patient. The antisynthetase syndrome consists of several characteristics, including ILD, arthritis, Raynaud phenomenon, "mechanic's hands," and positive antibodies to tRNA synthetases, which have each been negatively associated with cancer. When patients with DM present with such characteristics, clinicians may be falsely reassured that a thorough malignancy screen is unnecessary. We describe a patient who presented with the antisynthetase syndrome and was subsequently found to have colon cancer. Removal of the cancer led to resolution of the myositis and lung disease, but the patient's rash and arthritis persisted and ultimately required immunosuppressive therapy. We provide a review of the literature describing the concurrence of both this syndrome and ILD alone, with malignancy. We conclude that a thorough and expedited age-appropriate malignancy work up is indicated in all patients with a new diagnosis of DM, despite the presence of disease characteristics that are usually not associated with cancer.
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PMID:Malignancy in the setting of the anti-synthetase syndrome. 2212 9

We report three cases of complete response (CR) after treatment with UFT/LV for recurrent colorectal cancer. Case 1: A 44-year-old man was diagnosed with multiple liver metastases after resection of cecal cancer. UFT (500 mg/day)/Leucovorin (75 mg/day) was administered. Metastatic lesions of the liver completely disappeared on computed tomography(CT)one month after chemotherapy. Grade 2 hyperbilirubinemia and grade 1 diarrhea, pigmentation and rash were recognized. No signs of recurrence were observed for 35 months. Case 2: A 66-year-old man who underwent left colectomy and partial hepatectomy for transverse colon cancer and descending colon cancer with liver metastasis was determined to have multiple lung metastases. UFT/LV therapy was started. The lung lesions became only scars 7 months later. Adverse events were not seen. No other recurrence was found over 20 months. Case 3: A 66- year-old woman was detected with a lymph node recurrence after surgery for rectal cancer. CT revealed the disappearance of the tumor after 7 courses of UFT/LV therapy. Grade 2 hyperbilirubinemia appeared. Recurrence was not observed for 22 months, and the treatment has been discontinued.
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PMID:[Three cases of complete response after treatment with UFT and leucovorin for recurrent colorectal cancer]. 1901 50

Several trials show a relationship between skin toxicity, response rate, and overall survival in cetuximab-treated patients. We analyzed our database to evaluate the importance of skin rash as a surrogate marker of favorable outcome in cancer patients referred to our institution in the last three years. We retrospectively analyzed 90 cetuximab-treated patients: 57 colon cancer patients, 10 NSCLC patients, 14 locally advanced esophageal cancer patients, and 9 miscellaneous. A significant correlation was observed between skin rash and response to therapy. Skin rash was experienced by 93% of PR and 100% of CR patients. The mean TTP was 184 days in patients showing skin rash and 94 days in patients without skin rash, respectively. On multivariate analysis, skin rash was demonstrated to be the only independent prognostic variable with regard to TTP. Patients who did not develop skin rash had a 2-fold greater likelihood to manifest tumor progression significantly earlier than patients who developed skin rash. In our series, a statistically significant correlation between rash, response rate, and TTP was demonstrated in 90 cetuximab-treated patients. Skin toxicity was confirmed as the only clinical variable able to predict the response to cetuximab.
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PMID:Correlation between efficacy and skin rash occurrence following treatment with the epidermal growth factor receptor inhibitor cetuximab: a single institution retrospective analysis. 1928 4

Cerebellitis associated with herpes zoster has rarely been observed. We report here a 76-year-old man who had a history of anterior resection for sigmoid colon cancer and presented during chemotherapy with vesicular rash of the left ear, neuralgic pain in the postauricular area, and ataxic gait. After a while, he developed left peripheral facial palsy, fever, aggravated gait ataxia, and prolonged nausea and vomiting. The left facial nerve was enhanced on gadolinium-enhanced brain magnetic resonance imaging. We suspected that the patient had Ramsay Hunt syndrome accompanied by cerebellitis, which has not been reported previously. Over the course of several months, during which he was treated with acyclovir and corticosteroid, his symptoms improved significantly.
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PMID:A case of ramsay hunt syndrome complicated by cerebellitis. 2039 7


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