Poor prognosis germ cell tumors: current status and future directions.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
G C Toner
Publications and source records attributed to G C Toner.
Phase I trial of cremophor EL with bolus doxorubicin.
Cremophor EL (cremophor), a component of the paclitaxel formulation, can potentially reverse P-glycoprotein-associated multidrug resistance. A Phase I trial of cremophor as a 6-h infusion every 3 weeks was performed with bolus doxorubicin (50 mg/m2). The cremophor dose was escalated from 1 to 60 ml/m2. A standard paclitaxel premedication was given before cremophor. Using a bioassay, potentially active cremophor levels (> or = 1 microl/ml) were measured in plasma from patients receiving cremophor doses of 30, 45, and 60 ml/m2. A cross-over design was used to assess the influence of cremophor 30 ml/m2 on the pharmacokinetics of doxorubicin and doxorubicinol. The plasma area under the concentration versus time curve (AUC) of doxorubicin increased from 1448 +/- 350 to 1786 +/- 264 ng/ml x h (P = 0.02) in the presence of cremophor, whereas the AUC of doxorubicinol increased from 252 +/- 104 to 486 +/- 107 ng/ml x h (P = 0.02). This pharmacokinetic interaction was associated with significantly increased neutropenia. With reduction of the doxorubicin dose to 35 mg/m2, the cremophor dose was increased to 60 ml/m2. Dose-limiting toxicities occurred in two of six patients after 45 ml/m2 and two of four patients after 60 ml/m2, which included febrile neutropenia and grade III cremophor-related toxicities of rash, pruritus, headache, and hypotension. All patients who received 45 ml/m2 cremophor reached plasma levels > or = 1.5 microl/ml, but at 60 ml/m2, only two of four reached this level, and the calculated plasma clearance of cremophor was significantly faster at this dose. One patient with hepatoma resistant to epirubicin achieved a near-complete response. Cremophor 45 ml/m2 over 6 h with 35 mg/m2 doxorubicin is recommended for further studies. The pharmacokinetic interaction between cremophor and doxorubicin is quantitatively similar to that described in trials of paclitaxel with doxorubicin and suggests that the cremophor in the paclitaxel formulation is responsible.
Adult↗
Australian multicentre phase II trial of paclitaxel in women with metastatic breast cancer and prior chemotherapy.
OBJECTIVE: To determine the efficacy and safety of paclitaxel given as a three-hour infusion in patients with metastatic breast cancer which had progressed despite hormonal therapy and/or chemotherapy. DESIGN AND SETTING: Multicentre phase it trial undertaken in five major centres or hospitals in Sydney, Melbourne and Adelaide. PATIENTS AND METHODS: 50 patients with clinically or radiologically measurable or evaluable metastatic breast cancer recruited between March and July 1993. All had received prior chemotherapy, with subsequent disease progression. INTERVENTION: Paclitaxel (Anzatax, Faulding) was given at a dose of 175 mg/m2 intravenously over three hours every three weeks for up to nine courses. MAIN OUTCOME MEASURES: Response rate (partial or complete); duration of progression-free survival; duration of survival; and adverse reactions. RESULTS: Patients had a median age of 51 years; 62% had received at least two prior drug regimens for metastatic breast cancer and 48% had anthracycline-resistant tumours. A median of six paclitaxel courses was given per patient. Overall response rate was 18% (95% confidence interval [95% CI], 9%-31%), with complete responses in four patients (8%). In patients with anthracycline-resistant tumours, response rate was 25% (95% CI, 10%-47%). Response was not influenced by extent of prior treatment. Estimated median progression-free survival was 4.1 months (95% CI, 3.2-6.0 months) and estimated median survival was 6.3 months (95% CI, 6.2-10.3 months). Treatment was well tolerated, with neutropenia the major toxic effect. CONCLUSIONS: Paclitaxel (three-hour infusion) has significant activity in heavily pretreated patients with metastatic breast cancer, including anthracycline-resistant tumours.
Adult↗
Residual pulmonary masses after chemotherapy for metastatic nonseminomatous germ cell tumor. Prediction of histology. ReHiT Study Group.
BACKGROUND: After chemotherapy for a metastatic nonseminomatous germ cell tumor, pulmonary masses may be seen on a computed tomography scan. These residual masses may contain one of three histologic elements: necrosis, mature teratoma, or cancer. Because surgical resection of masses containing only necrosis is unnecessary, the authors aimed to predict the histology of these residual masses. METHODS: Six study groups contributed patient data on a total of 215 patients undergoing thoracotomy after cisplatin-based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumors. Logistic regression analysis was used to estimate the probability of necrosis, mature teratoma, and cancer in relation to predictors known before thoracotomy. RESULTS: The pulmonary mass histology was necrosis in 116 patients (54%), mature teratoma in 70 (33%), and cancer in 29 (13%). Necrosis was found at thoracotomy in 89% of those patients with necrosis at retroperitoneal lymph node dissection (RPLND). Other predictors included the primary tumor histology, prechemotherapy tumor marker levels, change in mass size during chemotherapy, and the presence of a single, unilateral mass. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > 0.20), which discriminated necrosis well from other histologies, especially if RPLND histology was available (area under the receiver operating characteristic curve, 0.86). CONCLUSIONS: This analysis indicated subgroups of patients with a high probability of necrosis and a low risk of cancer for whom close follow-up of the residual pulmonary mass might be considered. In most patients, a RPLND should be performed before a thoracotomy is considered, because the probability of necrosis is generally higher at thoracotomy than at RPLND and the histology at RPLND is a strong predictor of the histology at thoracotomy.
Analysis of Variance↗
Residual masses after chemotherapy for metastatic testicular cancer: the clinical implications of the association between retroperitoneal and pulmonary histology. Re-analysis of Histology in Testicular Cancer (ReHiT) Study Group.
PURPOSE: We determined the need and sequence of retroperitoneal lymph node dissection and thoracotomy in patients with nonseminomatous testicular cancer, and with residual retroperitoneal and pulmonary masses after chemotherapy. MATERIALS AND METHODS: We studied 159 patients undergoing retroperitoneal lymph node dissection and a thoracotomy following cisplatin based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumor. Several well-known predictors for residual histology (necrosis, mature teratoma and cancer) were evaluated. RESULTS: As expected, necrosis was found more often at retroperitoneal lymph node dissection if the primary tumor was negative for teratoma, the residual mass was small or the decrease in size was great. Contrary, neither residual mass size nor the decrease in size was predictive of the histological status of the residual lung lesion. Histological findings in the retroperitoneum and lung were strongly correlated, such that necrosis at retroperitoneal lymph node dissection was associated with an 89% probability of necrosis in the lung. CONCLUSIONS: Retroperitoneal lymph node dissection should be performed before thoracotomy is considered, since the histological status at dissection is a strong predictor of that at thoracotomy.
Germinoma↗
Chemotherapy for soft tissue sarcomas. Indications and advances.
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Adult↗
Phase I dose intensification study of 2-weekly epirubicin with GM-CSF in advanced cancer.
This study investigated dose intensification of epirubicin administered as a 2-weekly regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) support. The aim was to define the maximally tolerated dose of epirubicin and to assess the efficacy of GM-CSF to ameliorate its toxicity. Patients with anthracycline-responsive advanced malignancies were eligible. Six dose levels, commencing at 90 mg/m2, of epirubicin administered every 2 weeks for four courses were planned with GM-CSF 10 micrograms/kg/day administered for 10 days from the second day of each course. Six patients were to be entered at each dose level, and escalation to the next level was based upon toxicity criteria. Twelve patients were entered, six at dose level 1 (90 mg/m2) and six at dose level 2 (120 mg/m2). Prospectively defined haematological dose-limiting toxicities were noted in one patient at dose level 1 and in five patients at dose level 2. Further dose escalation was not attempted. Significant nonhaematological toxicities included febrile neutropenia in two and four patients at dose levels 1 and 2, respectively. This study has demonstrated that epirubicin can be safely administered at 2 week intervals with GM-CSF at a dose of 90 mg/m2, equivalent to the previously reported maximum tolerated dose intensity of 45 mg/m2/week. Neutropenia was dose-limiting despite the use of GM-CSF.
Adjuvants, Immunologic↗
Activity and toxicity of docetaxel (Taxotere) in women with previously treated metastatic breast cancer.
BACKGROUND: Metastatic breast cancer is a major cause of cancer death in Australian women. Docetaxel is a new cytotoxic drug that has shown promise in the treatment of metastatic breast cancer in patients who have previously received other chemotherapy, particularly an anthracycline, and has recently been approved for marketing in Australia. AIM: To report the first Australian experience with docetaxel in a group of women with metastatic breast cancer. METHODS: Patients with progressive metastatic breast cancer who had previously received other chemotherapy were treated with docetaxel 75 mg/m2 or 100 mg/m2 given as a one hour infusion every three weeks. All patients received oral dexamethasone for five days starting 24 hours prior to docetaxel as prophylaxis against fluid retention. The patients' response to docetaxel and toxicity were assessed by standard criteria. RESULTS: Twenty-six patients were treated. The major toxicity was neutropenia with 92% of patients experiencing at least one episode of grade 4 (absolute neutrophil count < 0.5 x 10(9)/L) neutropenia. Hospital admission for febrile neutropenia occurred in 44% of patients with one death from sepsis. Cumulative fluid retention was observed but in only one patient was it dose-limiting. Apart from alopecia, other toxicities were infrequent and rarely serious. In 23 patients assessable for response, there were 11 partial responses (48%). Three other patients whose disease could not be assessed for response had clinical improvement. The median survival of all patients treated was eight months. CONCLUSIONS: The response rate observed with docetaxel is comparable to that seen in trials in the United States and Europe and confirms the high activity of this new cytotoxic agent. Neutropenia is the major toxicity, and consideration should be given to the use of prophylactic oral antibiotics or colony stimulating factors to try and prevent febrile episodes. Clinicians will need to balance the benefits, toxicities, and cost of docetaxel in determining the appropriateness of its use in their patients.
Adult↗
Phase I trial of docetaxel and cisplatin in previously untreated patients with advanced non-small-cell lung cancer.
PURPOSE: To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacokinetics of the combination of docetaxel and cisplatin administered every 3 weeks to patients with advanced non-small-cell lung cancer (NSCLC) who have not received prior chemotherapy and to recommend a dose for phase II studies. PATIENTS AND METHODS: Patients with advanced NSCLC and performance status 0 to 2 who had not received prior chemotherapy received docetaxel over 1 hour followed by cisplatin over 1 hour with hydration. Dose levels studied were (docetaxel/cisplatin) 50/75, 75/75, 75/100, and 100/75 mg/m2 repeated every 3 weeks. Colony-stimulating factor (CSF) support was not used. Pharmacokinetics of docetaxel and cisplatin were studied in the first cycle of therapy. Most patients (79%) had metastatic disease or intrathoracic recurrence after prior radiation and/or surgery. RESULTS: Of 24 patients entered, all were assessable for toxicity and 18 for response. The MTD schedules were docetaxel 75 mg/m2 with cisplatin 100 mg/m2 (dose-limiting toxicities [DLTs] in five of six patients), and docetaxel 100 mg/m2 with cisplatin 75 mg/m2 (DLTs in two of two patients, including one fatal toxicity). Limiting toxicities were febrile neutropenia and nonhematologic, principally diarrhea and renal. Two patients had neutropenic enterocolitis. Pharmacokinetics of both drugs were consistent with results from single-agent studies, which suggests no major pharmacokinetic interaction. Neutropenia was related to docetaxel area under the plasma concentration-versus-time curve (AUC). An alternative schedule was investigated, with cisplatin being administered over 3 hours commencing 3 hours after docetaxel, but toxicity did not appear to be less. Independently reviewed responses occurred in eight of 18 patients (44%; 95% confidence interval, 22% to 69%), most following 75 mg/m2 of both drugs. CONCLUSION: Docetaxel 75 mg/m2 over 1 hour followed by cisplatin 75 mg/m2 over 1 hour is recommended for phase II studies. The responses seen in this phase I study suggest a high degree of activity of this combination in previously untreated advanced NSCLC.
Adult↗
Paclitaxel as first-line treatment for metastatic breast cancer. The Taxol Investigational Trials Group, Australia and New Zealand.
When administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard chemotherapy as front-line therapy for this disease. Patients with measurable or evaluable metastatic breast cancer, no prior chemotherapy for metastatic disease, and an Eastern Cooperative Oncology Group performance status of 0 to 2 were randomized to receive paclitaxel 200 mg/m2 intravenously over 3 hours for eight cycles (6 months) or standard treatment with oral cyclophosphamide (Cytoxan) 100 mg/m2/d days 1 through 14, intravenous methotrexate 40 mg/ m2 days 1 and 8, intravenous 5-fluorouracil 600 mg/m2 days 1 and 8, and oral prednisolone 40 mg/m2/d (CMFP) days 1 through 14 for six cycles (6 months). Patients whose disease progressed or relapsed were recommended to receive second-line epirubicin. Accrual has been completed with 208 patients randomized, but a preplanned interim analysis of the first 100 patients is reported here. Analysis of quality of life, assessed by a linear analogue scale and overall quality of life indices, is ongoing. Objective response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and 35% (confidence interval, 22% to 51%) with CMFP with stable disease in an additional 33% and 29%, respectively. Median time to progression was 5.5 months for paclitaxel-treated patients and 6.4 months for those given CMFP, with median survival durations of 17.3 and 11.3 months, respectively. Grades 3 and 4 neutropenia occurred in 64% of patients treated with paclitaxel and in 63% treated with CMFP. However, febrile neutropenia was the primary reason for hospitalization in 1% of paclitaxel courses, compared with 8% of CMFP courses. Nine percent of the patients had major infections with CMFP, but none were seen with paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel-treated and 27% of CMFP-treated patients. Alopecia and peripheral neuropathy were more common with paclitaxel. Quality of life assessments in the first 100 patients suggest better overall results on paclitaxel treatment as compared with CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated and provides comparable control of metastatic cancer to CMFP combination therapy when used as front-line treatment.
Antineoplastic Agents↗
Cremophor pharmacokinetics in patients receiving 3-, 6-, and 24-hour infusions of paclitaxel.
BACKGROUND: Paclitaxel (Taxol) is a new drug with efficacy against a variety of malignant tumors. The clinical formulation of paclitaxel contains 50% Cremophor EL, a polyethoxylated castor oil vehicle (carrier) that can reverse multidrug resistance (MDR) mediated by P-glycoprotein. Three-hour intravenous infusions of paclitaxel can yield end-of-infusion plasma Cremophor concentrations of 1 microL/mL or more, which are sufficient to reverse MDR in vitro by at least 50%. Despite extensive clinical use, the pharmacokinetics of Cremophor have not been described. PURPOSE: We studied the pharmacokinetics of Cremophor in patients with ovarian cancer who were undergoing treatment with paclitaxel to determine whether plasma Cremophor concentrations achieved during and following 3-, 6-, and 24-hour drug infusions were similar to those shown to modulate MDR in vitro. METHODS: Eleven patients with previously treated (i.e., with platinum-containing chemotherapy regimens) ovarian cancer were randomly assigned to receive one 3-hour, one 6-hour, and one 24-hour infusion of paclitaxel in varied sequences during their first three cycles of treatment with this drug. Blood samples were collected both during and following the three infusion periods, and Cremophor concentrations in these samples were measured by use of a bioassay based on the ability of Cremophor in plasma samples to reverse cellular resistance to daunorubicin in vitro. RESULTS: Ten patients were treated with paclitaxel at a dose level of 175 mg/m2, and one patient was treated at a dose level of 135 mg/m2. At the 175-mg/m2 dose level, peak plasma Cremophor concentrations of 1 microL/mL or more were achieved in eight of 10 patients during both the 3-hour and the 6-hour infusions; with the 24-hour infusion, only one patient achieved a peak plasma Cremophor concentration of 1 microL/mL or more. The eight patients who achieved plasma Cremophor concentrations of 1 microL/mL during the 3-hour infusion were above this level 30 minutes into the infusion; the total time that the plasma concentration was greater than 1 microL/mL was 8.9 +/- 5.0 hours (mean +/- standard deviation; range, 4.1-15.6 hours). For the eight patients who achieved plasma Cremophor concentrations of 1 microL/mL during the 6-hour infusion, the total time that the concentration was greater than 1 microL/mL was 10.2 +/- 9.0 hours (range, 0.3-21.9 hours). The patient who received paclitaxel at a dose of 135 mg/m2 achieved a peak plasma Cremophor concentration of 1 microL/mL or more only during the 3-hour infusion. CONCLUSIONS: Paclitaxel infusions of 3 and 6 hours can result in sustained plasma Cremophor concentrations sufficient for substantial reversal of P-glycoprotein-mediated MDR in vitro. These plasma Cremophor concentrations are not achieved during 24-hour infusions of paclitaxel.
Aged↗
Activity of gemcitabine in patients with advanced ovarian cancer: responses seen following platinum and paclitaxel.
Thirty-eight women with epithelial ovarian cancer were treated with gemcitabine, a new antimetabolite. All had previously received platinum, and 27 had also received paclitaxel. Four patients had a partial response giving a response rate of 13% in assessable patients (n = 31) and 11% for all patients entered. Additionally, 6 patients had stable disease with >50% reduction in CA-125 for at least 3 months. Activity was seen in patients resistant to both platinum and paclitaxel. Gemcitabine was well tolerated, with uncomplicated neutropenia the main hematological toxicity. Nonhematological toxicities were generally mild and included fatigue, myalgias, and skin rash. Gemcitabine has some activity in heavily pretreated ovarian cancer patients and deserves further investigation in this malignancy.
Adult↗
Association of acquired Pelger-Huet anomaly with taxoid therapy.
We describe the occurrence of acquired Pelger-Huet anomaly (APHA) in 23 patients treated with paclitaxel (13) or docetaxel (10). A consistent peak of Pelger-Huet cells (PHC) within a range of 3-9 d after treatment with taxoids was noted. The APHA generally disappeared by day 21 after treatment. Peak PHC values for the first course were significantly different in paclitaxel versus docetaxel versus control groups (P < 0.0001) with the maximum PHC counts being significantly higher for docetaxel compared with paclitaxel (P < 0.001) and for paclitaxel compared with controls (P = 0.007). We conclude that taxoid therapy produces transient APHA which peaks between days 3 and 9 and is more pronounced with docetaxel than with paclitaxel.
Adult↗
Carboplatin dosing based on measurement of renal function--experience at the Peter MacCallum Cancer Institute.
BACKGROUND: Carboplatin is used in treating many types of cancer. Because renal excretion is the major variable determining the pharmacokinetics of this drug, a dosing formula based on glomerular filtration rate (GFR) has been proposed and is being increasingly used in carboplatin dosing. This method of dosing is critically dependent on accurate measurement of GFR. AIMS: To report the experience at a single major oncology centre of carboplatin dosing based on GFR, and comparisons of different methods of measuring renal function for use in this dosing method. METHODS: An initial group of patients (n = 24) was studied where GFR was measured by Cr51EDTA clearance and compared to Tc99mDTPA clearance, measured 24 hour urine creatinine clearance and the Cockcroft and Gault formula. The carboplatin area under the plasma concentration versus time curve (AUC) was calculated using total platinum measured in a single blood sample assayed by flameless atomic absorption spectrophotometry. A subsequent patient group (n = 16) was then studied using Tc99mDTPA clearance to measure GFR. RESULTS: Carboplatin dosing using Cr51EDTA clearance to measure GFR was accurate (< 25% difference between planned and measured AUC) in 87% of samples. Estimation of renal function using the Cockcroft and Gault formula correlated with Cr51EDTA clearance only in patients with GFR < 100 mL/minute. The measured 24 hour urine creatinine clearance did not correlate with Cr51EDTA clearance. Using Tc99mDTPA clearance to measure GFR, carboplatin dosing was accurate in 81% of samples. Across a GFR range of 42-239 mL/minute, the Cr51EDTA and Tc99mDTPA clearance were closely correlated (r = 0.98, slope of regression line = 1.02). CONCLUSIONS: Carboplatin dosing using a pharmacological formula based on GFR produces accurate targeting of the carboplatin AUC. Tc99mDTPA clearance can be used to measure GFR instead of Cr51EDTA clearance, which is both more convenient and has potential cost savings. Estimates of renal function using the Cockcroft and Gault formula or measured 24 hour creatinine clearance are insufficiently accurate to use for carboplatin dosing.
Antineoplastic Agents↗
Paclitaxel (Taxol) as salvage therapy for relapsed ovarian cancer.
Thirty-two patients with epithelial ovarian cancer received paclitaxel 175 mg/m2, by 3-hour infusion, in this prospective phase 2 study. All patients had relapsed or progressed after initial cisplatin/cyclophosphamide therapy. Thirteen patients received paclitaxel as second line therapy, 14 as third line therapy and 5 as fourth line therapy. One patient was excluded from efficacy analysis, due to a severe anaphylactic reaction to the first cycle of paclitaxel therapy. Of the 31 evaluable patients, complete remission was observed in 3 patients (9.7%) and partial remission in 11 patients (35.5%), with a total response rate of 45.2%. The median survival from diagnosis for the 31 evaluable patients was 32.5 months and the median survival following therapy with paclitaxel was 12.2 months (range 4-27 months). The 3 patients who achieved a complete response remain alive, at greater than 20 months, since commencing paclitaxel. Twelve patients (38.7%) who achieved a partial response, or had stable disease, had a median survival, after paclitaxel treatment, of greater than 18 months. This study confirms the activity of paclitaxel in relapsed ovarian cancer and demonstrates a prolonged survival benefit in greater than one third of this group of patients.
Adult↗
Phase II trial of a 3-hour infusion of paclitaxel in previously untreated patients with advanced non-small-cell lung cancer.
PURPOSE: To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-one patients with advanced measurable or assessable NSCLC and performance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mg/m2 over 3 hours with premedication. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57%), extrathoracic metastatic disease (65%), and measurable disease (75%). Twenty-two percent had previously untreated stage III disease. RESULTS: The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organization (WHO) grade IV neutropenia in only 16% of patients. Grade III/IV myalgia/athralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred. CONCLUSION: The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase II trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.
Adult↗
Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic nonseminomatous germ cell tumor: multivariate analysis of individual patient data from six study groups.
PURPOSE: To develop a statistical model that predicts the histology (necrosis, mature teratoma, or cancer) after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT). PATIENTS AND METHODS: An international data set was collected comprising individual patient data from six study groups. Logistic regression analysis was used to estimate the probability of necrosis and the ratio of cancer and mature teratoma. RESULTS: Of 556 patients, 250 (45%) had necrosis at resection, 236 (42%) had mature teratoma, and 70 (13%) had cancer. Predictors of necrosis were the absence of teratoma elements in the primary tumor, prechemotherapy normal alfa-fetoprotein (AFP), normal human chorionic gonadotropin (HCG), and elevated lactate dehydrogenase (LDH) levels, a small prechemotherapy or postchemotherapy mass, and a large shrinkage of the mass during chemotherapy. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > .20), which discriminated necrosis well from other histologies (area under the receiver operating characteristic (ROC) curve, .84), but which discriminated cancer only reasonably from mature teratoma (area, .66). Internal and external validation confirmed these findings. CONCLUSION: The validated models estimate with high accuracy the histology at resection, especially necrosis, based on well-known and readily available predictors. The predicted probabilities may help to choose between immediate resection of a residual mass or follow-up, taking into account the expected benefits and risks of resection, feasibility of frequent follow-up, the financial costs, and the patient's individual preferences.
Analysis of Variance↗
The spectrum of 5-fluorouracil cardiotoxicity.
OBJECTIVE: To report three cases of cardiotoxicity related to the administration of 5-fluorouracil (5-FU) in patients with cancer. CLINICAL FEATURES: Three patients with gastrointestinal malignancies were being treated with combined radiotherapy and chemotherapy regimens. Two patients developed myocardial ischaemia and the other a ventricular arrhythmia in association with 5-FU administration. INTERVENTION AND OUTCOME: All patients survived the cardiac event. No patient was rechallenged with 5-FU. Radiotherapy was continued, achieving a good tumour response. CONCLUSION: Cardiotoxicity is rarely reported with 5-FU. The cardiac events can be life threatening. It is difficult to predict which patients will be affected. Clinicians need to be aware of this potential toxicity and monitor patients appropriately.
Adenoma↗