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Biomedical subjects

Weijing Sun

Publications and source records attributed to Weijing Sun.

At least 19 recordsLinked to original sources
PubMed2006

General assessment of the patient with cancer for the interventional oncologist.

Treating cancer involves more than high-tech regional and local therapies. To participate effectively in the care of patients with cancer, the interventional radiologist needs to have a basic understanding of all of the elements that make up the complete evaluation of the cancer patient. This understanding also facilitates interactions with other oncological experts that are necessary to care for these complex patients. Proper assessment of the patient is a key step in the treatment process.

Biomarkers, Tumor↗
PubMed2006

Oxaliplatin-associated hypersensitivity reactions: clinical presentation and management.

Hypersensitivity reactions to cisplatin and carboplatin have been reported in the literature to occur at a rate of 10%-27%. Initial reports of hypersensitivity reactions to oxaliplatin were low; however, more recently, it appears as if the incidence of hypersensitivity reactions to oxaliplatin is similar to that of the earlier generation platinum agents. The degree of the reaction varies from mild flushing to life-threatening anaphylactic responses. After a mild hypersensitivity reaction to oxaliplatin, re-exposing a patient can be considered after administering immunosuppressants (eg, high-dose corticosteroids and histamine antagonists) and/or prolonging the duration of oxaliplatin infusion. In the case of moderate-to-severe reactions to oxaliplatin, re-exposure is usually not considered, and alternative forms of therapy should be explored. However, there are reports of successful desensitization to oxaliplatin, and therefore, re-exposing a patient can be considered after carefully weighing the risks and benefits of additional oxaliplatin therapy.

Antineoplastic Agents↗
PubMed2005

Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281.

PURPOSE: Optimal treatments for metastatic carcinoid tumor remain undefined, and the role of chemotherapy for symptomatic patients with progressive disease is uncertain. PATIENTS AND METHODS: Two hundred forty-nine patients with advanced carcinoid tumors were randomized to either doxorubicin with fluorouracil (FU/DOX) or streptozocin with fluorouracil (FU/STZ). Patients crossed over to the dacarbazine (DTIC) treatment after disease progression following first-line treatment (either FU/DOX or FU/STZ), and 73 patients were assigned to one of these three treatments based on their previous treatment or on abnormal baseline cardiac or renal function. RESULTS: In the randomized group, there was no difference between FU/DOX and FU/STZ in response rates (15.9% v 16%) and progression-free survival (4.5 v 5.3 months). FU/STZ (24.3 months) was superior to FU/DOX (15.7 months; P = .0267) in median survival. The response rate of crossover DTIC treatment was 8.2%, with a median survival of 11.9 months. Hematologic toxicities were the major treatment-related toxicities for both FU/DOX and FU/STZ, and mild to moderate renal toxicity was reported in 40 (34.8%) of 115 patients in the FU/STZ arm. CONCLUSION: Response to all three treatment regimens were modest. FU/STZ improved survival compared with the doxorubicin-based regimen, suggesting that the combination should be considered to be an active regimen of therapy when chemotherapy is judged to be an option for selected patients with carcinoid tumors.

Adult↗
PubMed2005

Phase I trial of combretastatin a-4 phosphate with carboplatin.

PURPOSE: Preclinical evidence of synergy led to a phase I trial employing combretastatin A-4 phosphate (CA4P), a novel tubulin-binding antivascular drug, in combination with carboplatin. EXPERIMENTAL DESIGN: Based on preclinical scheduling studies, patients were treated on day 1 of a 21-day cycle. Carboplatin was given as a 30-minute i.v. infusion and CA4P was given 60 minutes later as a 10-minute infusion. RESULTS: Sixteen patients with solid tumors received 40 cycles of therapy at CA4P doses of 27 and 36 mg/m(2) together with carboplatin at area under the concentration-time curve (AUC) values of 4 and 5 mg min/mL. The dose-limiting toxicity of thrombocytopenia halted the dose escalation phase of the study. Four patients were treated at an amended dose level of CA4P of 36 mg/m(2) and carboplatin AUC of 4 mg min/mL although grade 3 neutropenia and thrombocytopenia were still observed. Three lines of evidence are adduced to suggest that a pharmacokinetic interaction between the drugs results in greater thrombocytopenia than anticipated: the carboplatin exposure (as AUC) was greater than predicted; the platelet nadirs were lower than predicted; and the deviation of the carboplatin exposure from predicted was proportional to the AUC of CA4, the active metabolite of CA4P. Patient benefit included six patients with stable disease lasting at least four cycles. CONCLUSION: This study of CA4P and carboplatin given in combination showed dose-limiting thrombocytopenia. Pharmacokinetic/pharmacodynamic modeling permitted the inference that altered carboplatin pharmacokinetics caused the increment in platelet toxicity.

Adult↗
PubMed2005

Adjuvant therapy for colon cancer.

As there have been advances in the treatment of metastatic colorectal cancer, exciting developments have also been achieved in the adjuvant treatment of colon cancer. At the same time, more questions have been raised, and some controversies remain. The results of the MOSAIC trial demonstrated the benefit of adding oxaliplatin to 5-fluorouracil (5-FU) and leucovorin (FOLFOX) in adjuvant therapy for stage II and III disease, but the optimal duration of therapy and the management of toxicities remain to be resolved. Capecitabine is at least equivalent to the Mayo Clinic bolus 5-FU and leucovorin regimen in the adjuvant treatment of stage III colon cancer with a lower incidence profile of adverse events, allowing additional options for patients and physicians. Routine adjuvant systemic therapy in all patients with stage II colon cancer is still debatable. Although a statistically significant advantage for adjuvant treatment in stage II disease was shown for the first time from a large randomized study (QUASAR), the subsets of patients who truly benefit from therapy need to be identified. The application of pharmacogenetics and pharmacogenomics in adjuvant therapy for colorectal cancer will help to distinguish those patients with risk factors and to guide individualized therapy.

Antineoplastic Agents↗
PubMed2005

Adjuvant therapy of colon cancer.

Although surgical resection is still the only curative maneuver in the treatment of colon cancer, efforts of the past decades have proved that systemic chemotherapy in the adjuvant setting definitely improves the curative rate for those patients with localized colon cancer. The combination of the 5-fluorouracil (5-FU) and leucovorin (LV) remains the reference treatment. However, the advantage of infusional 5-FU/LV with oxaliplatin (FOLFOX) as adjuvant treatment may change the paradigm soon. Capecitabine may be considered as an alternative to 5-FU/LV in the adjuvant therapy of stage III colon cancer. The clinical benefit of adjuvant chemotherapy for localized node negative (stage II) disease is definite but small, even though there is yet no universal consensus. Novel molecular and biologic-oriented agents are being studied. Further analysis and definition of prognostic and predictive markers may allow future adjuvant therapy to be individualized.

Antibodies, Monoclonal↗
PubMed2004

Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome.

Appropriate patient selection is crucial in ensuring acceptable outcomes from orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The United Network for Organ Sharing (UNOS) has elected to prioritize HCC patients for OLT based on criteria of tumor burden. However, it is unclear whether these criteria correlate with outcome, or with the pathobiological features associated with tumor recurrence. Therefore, we analyzed 109 consecutive patients undergoing OLT for HCC at our center, to determine the utility of present selection criteria in predicting outcome. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified tumor node metastases (pTNM) classification system. Multifocality was defined as >4 tumor nodules on explant. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression methods. At a median follow-up of 18.9 months, the overall mortality was 19% with 15 patients (14%) dying of recurrent HCC. Kaplan-Meier 1, 3 and 5-year survival rates were 89.5%, 68%, and 65%, respectively. Recurrence-free rates of 1, 3, and 5 years were 89%, 75%, and 65%, respectively. On univariate analysis, the factors found to be significantly associated with recurrence of HCC were explant features of macrovascular invasion, tumor size (per centimeter increase), pTNM stage (per 1-stage increase), and pre-transplant serum alphafetoprotein (AFP) >300 ng/mL. In defining a threshold level, we found that explant tumor diameter > or =3 cm, and those tumors classified as at least pT3 on pathological examination, were significantly associated with recurrence (P =.01 and.03, respectively). Tumor size on explant was found to be strongly correlated with multifocality (P =.017) and vascular invasion (P =.02). Patients exceeding pathological UNOS criteria were 3.1 times more likely to have recurrence of HCC (P =.03). In conclusion, we found that tumor size appears to be a surrogate marker for negative pathobiological predictors of outcome, i.e., vascular invasion and multifocality. Present UNOS selection criteria for HCC based on tumor burden appear to provide adequate discriminatory power in predicting outcome of OLT.

Adult↗
PubMed2004

Concurrent RT with 5-FU/epirubicin and cisplatin or irinotecan for locally advanced upper GI adenocarcinoma.

From the results of recent studies, it is likely that multimodality therapy with chemotherapy and radiation treatment may improve the overall outcome of locally advanced upper gastrointestinal (GI) malignancies, including esophageal, gastric, pancreatic, and biliary tract carcinomas. However, more effective, more optimal, and less toxic chemotherapy regimen(s) with concomitant radiotherapy are needed beyond the concurrent continuous-infusion fluorouracil (5-FU) with radiation that is commonly applied in general practice. Epirubicin (Ellence), cisplatin, and irinotecan (Camptosar) are all active cytotoxic chemotherapy agents in upper GI cancers. Two phase I studies were designed to test the tolerability of the combination of radiotherapy with infusional 5-FU, epirubicin, and cisplatin (ECF) or 5-FU, irinotecan, and epirubicin (EIF) in the treatment of locally advanced upper GI malignancies.

Adenocarcinoma↗
PubMed2003

Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow.

PURPOSE: Combretastatin A4 (CA4) phosphate (CA4P) inhibits microtubule polymerization and is toxic to proliferating endothelial cells in vitro. It causes reversible vascular shutdown in established tumors in vivo, consistent with an antivascular mechanism of action. The present study investigated escalating doses of CA4P administered intravenously to patients with advanced cancer. PATIENTS AND METHODS: Patients with solid malignancies and good performance status received CA4P as a 10-minute infusion daily for 5 days repeated every 3 weeks. Pharmacokinetic sampling was performed during cycle 1. Patients receiving >/= 52 mg/m2/d had serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies to measure changes in tumor perfusion with CA4P treatment. RESULTS: Thirty-seven patients received 133 treatment cycles. CA4P dose levels ranged from 6 mg/m2 to 75 mg/m2 daily. Severe pain at sites of known tumor was dose limiting at 75 mg/m2. Dose-limiting cardiopulmonary toxicity (syncope and dyspnea or hypoxia) was noted as well in two patients treated at 75 mg/m2. Other toxicities included hypotension, ataxia, dyspnea, nausea or vomiting, headache, and transient sensory neuropathy. Plasma CA4P and CA4 area under the concentration-time curve and maximal concentration values increased linearly with dose. Tumor perfusion, as measured by the first-order rate constant of gadolinium plasma to tissue transfer during DCE-MRI studies, was found to decrease in eight of 10 patients. Relationships were also demonstrated between perfusion changes and pharmacokinetic indices. A partial response was observed in a patient with metastatic soft tissue sarcoma, and 14 patients exhibited disease stability for a minimum of two cycles. CONCLUSION: Doses of CA4P on a daily times five schedule of 52 to 65 mg/m2 were reasonably well-tolerated. The 52 mg/m2 dose is recommended for further study based on cumulative phase I experience with CA4P. Antitumor efficacy was observed, and the use of DCE-MRI provided a valuable noninvasive measure of the vascular effects of CA4P treatment.

Adult↗
PubMed2003

Phase I and pharmacokinetic trial of the novel taxane BMS-184476 administered as a 1-hour intravenous infusion in combination with cisplatin every 21 days.

BMS-184476 is a 7-methylthiomethyl ether derivative of paclitaxel that displays potency superior to paclitaxel against tumor cells in culture and human tumor xenografts. It also inhibits the growth of paclitaxel-resistant human tumor cell lines with multidrug resistance mediated by either P-glycoprotein or mutated tubulin. Given the known synergy between taxanes and cisplatin in vitro and their clinical activity in combination, we performed a Phase I trial of BMS-184476 as a 1-h i.v. infusion followed by cisplatin every 21 days. Twenty-seven patients with a variety of solid tumors and good performance status received 116 cycles of therapy at BMS-184476 doses of 40-60 mg/m(2) together with cisplatin at 75 mg/m(2). The early observation of hypersensitivity reactions required prophylactic premedication in all patients. At the planned highest dose of BMS-184476 (60 mg/m(2)) and cisplatin (75 mg/m(2)), we observed dose-limiting toxicity in the form of neutropenia and diarrhea. Also at this level, five patients experienced grade 3 or worse nausea and vomiting. Aggressive prophylactic treatment eliminated the gastrointestinal toxicity. Mild to moderate peripheral neuropathy was infrequent, as was alopecia. Patient benefits included three partial responses in patients with mesothelioma, esophageal cancer, and head and neck cancer, and two additional minor responses. Plasma pharmacokinetic data are available for 23 patients treated at 40-60 mg/m(2). The mean maximum plasma concentrations and areas under the curves increased in a dose-related manner. The pharmacokinetics of BMS-184476 appeared independent of dose. The mean (+/- SE) values for clearance, volume of distribution at steady state, and the apparent terminal half-lives of the three dose groups during cycle 1 were 243 +/- 5 ml/min/m(2), 423 +/- 58 l/m(2), and 32.2 +/- 4.5 h, respectively. BMS-184476 60 at mg/m(2) with cisplatin at 75 mg/m(2) with appropriate supportive therapy is the dose recommended for further evaluation.

Adult↗
PubMed2003

Dose escalation study of tezacitabine in combination with cisplatin in patients with advanced cancer.

BACKGROUND: The authors performed a dose escalation study of cisplatin and the novel deoxycytidine analog, tezacitabine, to determine the maximum tolerated dose of the combination. METHODS: Twenty-three patients with advanced cancer and good performance status were accrued to 3 dose levels of tezacitabine (150-270 mg/m(2)) and cisplatin (50 mg/m(2)). Using a 28-day treatment cycle, both drugs were administered on Days 1 and 15. RESULTS: Hematologic toxicity was the most frequently observed side effect and was dose limiting. Grade 3 or 4 neutropenia and thrombocytopenia complicated 75% and 31% of all cycles, respectively. Nonhematologic toxicities were mild. Among 18 evaluable patients, 2 with upper gastrointestinal tract tumors achieved partial responses and 4 had stable disease. CONCLUSIONS: Based on dose-limiting neutropenia and thrombocytopenia at the highest dose level, the recommended Phase II doses are 200 mg/m(2) of tezacitabine and 50 mg/m(2) of cisplatin.

Adult↗
PubMed2003

Irinotecan and fixed-dose-rate gemcitabine in advanced pancreatic and biliary cancer: phase I study.

It is a continuing challenge for oncologists to effectively treat advanced/metastatic pancreatic and biliary cancer. Both irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have shown activity against these diseases with different mechanisms. Preclinical and clinical data also suggest additive or synergistic effects of the combination of these two agents with few or no overlapping toxicities. Phosphorylation of gemcitabine, a process of intracellular activation of the agent, is dose-rate dependent. It has been suggested that the fixed-dose-rate infusion of gemcitabine increases the concentration of intracellular triphosphate gemcitabine, which in turn may result in more objective responses and longer median survival compared to the standard infusion. This phase I study tests the toxicity of the combination of irinotecan with fixed-dose-rate infusion of gemcitabine, and determines the dose of the combination for phase II investigation.

Adenocarcinoma↗
PubMed2002

Chemotherapy for colorectal cancer.

With effective chemotherapy as adjuvant treatment, the survival benefit is clearly achieved for certain (stage III) colorectal cancer patients, though there still exist many unsettled issues including the controversies in the treatment of stage II disease. Advances in the development of a new generation of cytotoxic agents in the past several years have allowed us to move forward from the "fluorouracil-only era" in the treatment of advanced/metastatic colorectal cancer. It is still not very clear how best to minimize toxicity without compromising efficacy of the combination therapy with newer agents, or how to maximize the benefit of chemotherapy (concurrent versus sequential). There are many current ongoing clinical trials designed to address these issues. With better understanding of the signal transduction and molecular biology characteristics of colorectal cancer, and the development of biologic and molecular target agents, the outcomes of patients with colorectal cancer will be improved further. Future clinical trials should be focused on optimizing and individualizing therapy for patients based on their molecular profiles to achieve maximal clinical benefit.

Antineoplastic Agents↗
PubMed2002

Phase I trial of the cryptophycin analogue LY355703 administered as an intravenous infusion on a day 1 and 8 schedule every 21 days.

The cryptophycin analogue LY355703 is a potent inhibitor of microtubule polymerization that displays in vitro and in vivo activity in cell lines and tumor xenografts displaying the multidrug-resistant phenotype. In a Phase I trial, 25 patients received LY355703 as a 2-h i.v. infusion on day 1 and day 8 repeated every 3 weeks. Doses were escalated from 0.1 to 2.22 mg/m2 using a modified continual reassessment method. Neurological toxicity was found to be dose-limiting at 1.84 and 2.22 mg/m2. Among four patients treated at these doses, two had grade 4 constipation/ileus, one with severe myalgias, and one had grade 3 motor neuropathy. These findings were reversible. The 1.5 mg/m2 dose level was well tolerated. An amended twice-weekly schedule was pursued in 11 patients in an attempt to improve dose intensity and avoid dose-limiting neurotoxicity. Doses of >0.75 mg/m2 on a day 1, 4, 8, and 11 schedule every 21 days were not tolerated as a result of nausea/constipation, suggesting that LY335703 toxicity is not schedule dependent and is related to cumulative dose. LY355703 plasma concentrations measured by liquid chromatography with tandem mass spectrometry were evaluated using a population pharmacokinetic model. LY355703 was eliminated rapidly with a short terminal half-life that ranged from 0.8 to 3.9 h. Interpatient variability with respect to plasma clearance and volume of distribution, including covariates, was moderate at 32% and 39%, respectively. Maximum plasma concentration and area under the plasma concentration-time curve were linear over the dose range studied. A patient with non-small cell lung cancer previously treated with taxanes experienced a partial response lasting 4 months, and five patients had stable disease lasting > or =3 months. LY355703 at a dose of 1.5 mg/m2 is recommended for Phase II evaluation on a days 1 and 8 schedule. Twice-weekly dosing did not allow improvement in dose intensity or tolerability.

Adult↗