Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The safety and pharmacology of the intraperitoneal administration of Taxol was evaluated by treatment of 25 patients (24 with ovarian cancer) on a phase I dose-escalation trial. The drug was delivered in 2 L of normal saline every 3 to 4 weeks, with a starting dose of 25 mg/m2. The dose-limiting toxicity was abdominal pain at Taxol doses greater than 125 mg/m2. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to Taxol, compared to the systemic compartment, was demonstrated following intraperitoneal delivery. In addition, high levels of Taxol persisted within the cavity for more than 48 hours following a single treatment. Despite the major pharmacokinetic advantage for peritoneal cavity exposure, significant concentrations of Taxol were demonstrated within the systemic compartment after intraperitoneal treatment. Several patients exhibited clinical and laboratory evidence of an antitumor response. Further exploration of a possible role for the intraperitoneal administration of Taxol in the management of ovarian cancer appears indicated.
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PMID:Intraperitoneal administration of Taxol in the management of ovarian cancer. 791 15

Paclitaxel, a recently approved antineoplastic agent, is cleared slowly from the peritoneal cavity after i.p. injection, and therefore appears to be promising for intracavitary therapy of malignancies confined to the peritoneal cavity. However the dose-limiting toxicity of Taxol, the clinical formulation of paclitaxel, was severe abdominal pain, likely caused by the excipients (Cremophor EL and ethanol) that are required to overcome low drug solubility. We tested the hypothesis that a liposome-based formulation could modulate paclitaxel toxicity independent of antitumor activity. The dose-dependence of toxicity and antitumor effect of paclitaxel liposomes was evaluated after i.p. administration against i.p. P388 leukemia. Liposomal paclitaxel showed antitumor activity similar to that of free paclitaxel (as Taxol), but was better tolerated by both healthy and tumor-bearing mice.
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PMID:Paclitaxel-liposomes for intracavitary therapy of intraperitoneal P388 leukemia. 894 23

An effective local-regional therapy is needed for adenocarcinomas of the pancreas. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton NJ) may enhance the effect of radiation therapy. Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent radiation (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer (NSCLC). This suggested that paclitaxel/RT was a rationale treatment approach for other malignancies which frequently harbor p53 mutations such as upper gastrointestinal malignancies. We have completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancers. The maximum tolerated dose (MTD) of paclitaxel was 50 mg/m2/week for 6 weeks with abdominal radiation. The dose limiting toxicities were abdominal pain within the radiation field, nausea and anorexia. Twenty-five patients with locally advanced pancreatic cancer have now completed treatment at the phase II dose level of paclitaxel 50 mg/m2/week with 50 Gy concurrent RT. Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions in 2 patients, asymptomatic grade 4 neutropenia in 3 patients, and non-neutropenic biliary sepsis in 1 patient. Of the first 22 assessable patients treated at the phase II study, 8 obtained a partial response (PR) for a preliminary response rate of 36%. These findings demonstrate that paclitaxel/RT is well tolerated with substantial activity for locally advanced pancreatic cancer.
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PMID:Paclitaxel and concurrent radiation for locally advanced pancreatic carcinoma. 979 3

An effective locoregional therapy is needed for adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) may enhance the effect of radiation therapy (RT). Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent RT (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer. This finding suggested that paclitaxel/RT was a rational treatment approach for other malignancies that frequently harbor p53 mutations, such as upper gastrointestinal malignancies. We completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancer. The maximum tolerated dose of paclitaxel was 50 mg/m2/wk for 6 weeks with abdominal RT. The dose-limiting toxicities were abdominal pain within the radiation field, nausea, and anorexia. Phase II studies are now under way. Twenty-five patients with locally advanced pancreatic cancer have been entered at the phase II dose level of paclitaxel 50 mg/m2/wk with concurrent RT (total dose, 50 Gy). Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions (n = 2), asymptomatic grade 4 neutropenia (n = 3), and nonneutropenic biliary sepsis (n = 1). Of the first 18 assessable patients with pancreatic cancer treated on the phase II study, six obtained a partial response, for a preliminary response rate of 33%. In the phase II study for locally advanced gastric cancer, 20 patients have been enrolled. Of the first 19 patients who have completed treatment, nine (47%) had grade 3/4 toxicities, including nausea, anorexia, esophagitis, and gastritis. Of the first 16 patients with gastric cancer, complete and partial responses have been observed in one and eight patients, respectively, for a preliminary response rate of 56%. We have also completed treatment on 24 patients with potentially resectable adenocarcinomas of the gastroesophageal junction with neoadjuvant paclitaxel 60 mg/m2 and cisplatin 25 mg/m2, weekly for 4 weeks, with concurrent RT (total dose, 40 Gy) followed by surgical resection. Ten patients (41%) had grade 3/4 toxicities, including neutropenia, nausea, and dehydration. Of 24 patients, four complete responses (17%) and 14 partial responses (58%) were observed, for an overall response rate of 75%. Severe esophagitis was uncommon, making this a well-tolerated outpatient regimen for adenocarcinomas of the distal esophagus. These findings demonstrate that paclitaxel-based chemoradiation for locally advanced upper gastrointestinal malignancies is well-tolerated with substantial activity.
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PMID:Paclitaxel and concurrent radiation therapy for locally advanced adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. 1021 May 40

The current study presents the case of a 68-year-old female patient who received biological intensity-modulated radiotherapy (BIMRT) and neoadjuvant chemotherapy for multiple peritoneal metastases of ovarian cancer. The International Federation of Gynecology and Obstetrics disease stage was IIIc. In addition, the patient presented with urination and defecation difficulties. The result of tumor marker detection showed a carcinoembryonic antigen level of 348.2ng/ml, a cancer antigen 125 level of 2,091 U/ml and a cancer antigen 19-9 level of 113 U/ml. Computed tomography (CT) indicated and ovarian cystic or solid package, enlargement of multiple abdominal and retroperitoneal lymph nodes and abdominal cavity effusion. Positron emission tomography/CT indicated multiple internal organ metastases. The center of the ovarian cystic or solid package was considered to be a malignant tumor. A large amount of ascites were detected, as well as abdominal and retroperitoneal lymph node metastasis. The patient was treated with BIMRT at a total dose of 48 Gy, administered as a single 4.0-Gy dose 12 times. In addition, 100 mg cisplatin was administered as a peritoneal perfusion, followed by two cycles of 180 mg Taxol and 100 mg cisplatin. Furthermore, the enlargement of the lymph nodes was reduced and the tumor in the region of the ovary had decreased in size by 90%. The ascites had disappeared and the abdominal pain was greatly improved. At the time of writing this manuscript, the patient was well and without relapse. Therefore, modern radiotherapy techniques, such as BIMRT, may be considered as a beneficial treatment option for ovarian cancer patients with multiple peritoneal metastases in whom surgery is not suitable.
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PMID:Biological intensity-modulated radiotherapy plus neoadjuvant chemotherapy for multiple peritoneal metastases of ovarian cancer: A case report. 2566 90

The authors present the history of a 48-year-old woman, who developed pleural effusion, abdominal pain and ascites due to an advanced ovarian cancer. She underwent hysterectomy and bilateral adnexectomy in 2006, and histology revealed FIGO IIIB papillary adenocarcinoma. After surgery the patient recieved the standard, 6 cycle taxol-carboplatin therapy. Taxol-carboplatin therapy was reinitiated because of retroperitoneal lymph node metastases in 2008, but soon the therapy had to be changed because of progression. Thereafter the patient recieved 6 different types of chemo- and biological therapy including the off-label FOLFOX-4 treatment at seventh line. Significant regression in response to FOLFOX-4 therapy was confirmed with a progression free survival of about 9 months. The general condition of the patient was satisfying during the whole chemotherapy, and the side effects were tolerable. The overall survival was 98 months. This case history is a good example for the success of individualized, long term chemotherapy even if ovarian tumor diagnosed at advanced stage as it happened in this case. Orv. Hetil., 2016, 157(44), 1769-1773.
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PMID:[Chemotherapeutic treatment of metastatic ovarian cancer for 8 years. Case report]. 2779 25

BACKGROUND Hepatic metastasis is well known in breast cancer. Approximately 12-20% of breast cancer patients will develop liver metastasis, which usually presents as discrete mass lesions. Rarely, metastatic spread can be so diffuse that it is unidentifiable on imaging but can progress to fulminant hepatic failure. Our case report suggests that clinicians need to have a high index of suspicion when patients present with rapidly decompensating liver failure in the absence of discrete radiologic hepatic lesions, and that weekly Adriamycin should be considered as a first-line therapeutic option. CASE REPORT A 28-year-old African American woman with a history of locally advanced estrogen receptor-positive, progesterone receptor-negative, and HER2-negative breast cancer presented with right upper quadrant abdominal pain and bilateral lower extremity swelling. She had been treated 3 years prior with neoadjuvant Adriamycin/cyclophosphamide - Taxol, bilateral mastectomies, radiation therapy, and tamoxifen. Diagnostic imaging revealed massive hepatomegaly and extensive areas of liver ischemia/necrosis without discrete masses or arterial/venous thrombosis. Biopsy of the liver revealed metastatic carcinoma diffusely infiltrating the hepatic sinusoids. Extensive work up for other etiologies of liver disease was negative. The patient's liver function quickly decompensated over several days. She was treated with weekly single-agent low-dose Adriamycin, and this resulted in successful reversal of her liver function tests back to baseline. CONCLUSIONS In addition to having a high index of suspicion for diffuse intrasinusoidal hepatic metastasis, physicians should consider weekly low-dose Adriamycin as a first-line therapeutic option for patients with progressive liver failure and biopsy-confirmed metastatic carcinoma diffusely infiltrating the hepatic sinusoids.
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PMID:Diffuse Intrasinusoidal Hepatic Metastasis from Breast Cancer Presenting as Liver Failure: Effective and Rapid Treatment with Weekly Low-Dose Adriamycin. 3287 89