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PubMed2004

A phase II trial of neoadjuvant docetaxel and capecitabine for locally advanced breast cancer.

PURPOSE: This study evaluated the toxicity and efficacy of docetaxel/capecitabine as neoadjuvant treatment for stage 2/3 breast cancer. EXPERIMENTAL DESIGN: Subjects with newly diagnosed invasive stage 2 and 3 breast cancer were eligible. The first cohort of patients was treated at dose A with neoadjuvant docetaxel (75 mg/m(2) i.v. day 1) and capecitabine (1000 mg/m(2) orally twice daily days 2-15) for four cycles. A second cohort of subjects was treated with a reduced dose, dose B, of docetaxel (60 mg/m(2) i.v. day 1) and capecitabine (937.5 mg/m(2) orally twice daily days 2-15). RESULTS: Thirty patients were enrolled. Eight of 10 patients treated at dose A required dose reductions of either docetaxel or capecitabine secondary to grade 3 or 4 toxicities: mucositis (1), hand-foot syndrome (3), diarrhea (2), perirectal abscess (1), and neutropenia (2). Because of a high rate of dose reductions, the next 20 patients were treated at dose B. The mean cumulative administered dose of docetaxel was 285 and 231 mg/m(2) at dose A and dose B, respectively. For capecitabine, the mean cumulative dose at dose A and B were similar at 1585 and 1627 mg/m(2)/day, respectively. The overall clinical response rate was 90% with 31% of patients having a complete response and 59% having a partial response. A pathological complete response in the breast was achieved in 10% of patients after four cycles of docetaxel/capecitabine. CONCLUSIONS: Docetaxel/capecitabine is a highly active regimen in the neoadjuvant setting. Neoadjuvant therapy with 75 mg/m(2) docetaxel and 1600 mg/m(2)/day days 2-15 is recommended.

Administration, Oral↗
PubMed2005

Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours.

In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against gamma-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 +/- 2% (p-value <0.001) was observed in the rat brain-this may account for neurological and behavioural abnormalities found in mammals drinking highly deuterated water. In addition to characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this report also estimates the impact of oedema on thermal neutron enhancement and effective dose reduction factors using simple linear transport calculations. While body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as approximately 10% in the presence of a 9% water volume increase (oedema).

Administration, Oral↗
PubMed2004

Weekly 5-fluorouracil and leucovorin: achieving lower toxicity with higher dose-intensity in adjuvant chemotherapy after colorectal cancer resection.

BACKGROUND: Current standard therapy following resection of high-risk colon cancer is intravenous bolus 5-fluorouracil (5-FU) with leucovorin (LV), but there is no consensus on the optimum regimen of these drugs: practice ranges from the high toxicity Mayo Clinic schedule to the very low toxicity weekly QUASAR schedule. We present data for a weekly schedule that aims to provide moderately dose-intense treatment with low toxicity. PATIENTS AND METHODS: One hundred and sixty-two patients were studied: 60% male; median age 65 years (36% over 70 years); 94% colorectal primary. Treatment was intravenous bolus (5 min) 5-FU 425 mg/m(2) plus D,L-LV 45 mg flat rate once weekly, for a planned 24 weeks. Data for toxicity, dose-reductions, delays and stoppages were collected. RESULTS: Overall, 20% of patients experienced any grade > or = 3 toxicity, most commonly diarrhoea (14% patients). Dose reductions were made in 35% of patients (although only 21% required 20% or more reduction); toxicity contributed to a decision to stop treatment before 24 weeks in 16% of patients. Median delivered dose intensity (DI) was 96% of planned (407 mg/m(2)/week) during treatment, and 91% of planned (385 mg/m(2)/week) over the full 24 week treatment plan. Female sex and age >70 years were significantly associated with higher rates of toxicity and dose adjustment, and lower delivered DI. CONCLUSIONS: Weekly treatment at these doses is convenient and well-tolerated for the large majority of patients, and achieves DI comparable with the 5 days a month QUASAR schedule and other more toxic standard regimens.

Adult↗
PubMedDate not supplied

Ytterbium-169: a promising new radionuclide for intravascular brachytherapy.

PURPOSE: To explore the feasibility of 169Yb (gamma, 93 keV) as a new radionuclide for intravascular brachytherapy (IVBT) in terms of dose distribution, penetration power, and radiation safety features as compared with 125I and 192Ir. METHODS: The dose distributions for catheter-based sources, 169Yb, 125I, and 192Ir, in homogeneous water and in the presence of calcium and a steel stent have been determined and compared using the Monte Carlo method (MCNP4B2 code). The dose rates of the sources were evaluated from 0.02 to 100 cm. RESULTS: In the short distance range (0.02<r<1.0 cm), the dose distributions in homogeneous water are very similar for the three radionuclides when the dose rates are normalized at 2 mm. Between 1 and 20 cm, the relative dose rates fall off similarly for 169Yb and 192Ir, whereas for 125I, it decreases much more rapidly. At a distance further away (r approximately 100 cm), the dose rate of 169Yb is about 10 times lower than that of 192Ir, indicating the cathlab radiation shielding requirement for 169Yb is substantially reduced as compared with 192Ir. Calcified plaques and stents cause a drastic dose reduction in the arterial wall for 125I, but have no effect for 192Ir gamma-rays. Only slight dose reductions were detected for 169Yb beyond a layer of 1.0-mm calcium (2-3%), and behind a steel stent strut (5%). CONCLUSION: 169Yb is a promising new radionuclide for IVBT. It has a much better penetrating power through calcified plaques and stents compared with the low-energy source 125I. It also provides easier radiation protection measures for cardiac cathlab personnel than the high-energy source 192Ir, while preserving a favorable dose distribution in tissues surrounding an arterial vessel.

Brachytherapy↗
PubMed2000

Experience with continuous infusion of recombinant activated factor VII in the Asia-Pacific region.

There is increasing interest in continuous infusion of recombinant activated factor VII (rFVIIa) as a convenient and safe alternative to intermittent bolus therapy. In the Australian patients reported in this paper, cost savings of up to 25% in the first 12 h of treatment with continuous infusion of rFVIIa have been achieved safely, suggesting that substantial overall savings are possible. However, in the Thai patient reported, a dose reduction of 35% in the first 12 h was associated with poor haemostatic control, suggesting that a dose reduction of >25% may be inadvisable. The indications for treatment in the five Australian patients were: retroperitoneal haemorrhage (n = 3); right forearm compartment syndrome (n = 1); wrist haemarthrosis and median nerve compression (n = 2); sublingual haematoma (n = 1); and cerebral (mid-brain) haemorrhage (n = 1). Treatment was effective in four out of five patients (six bleeding episodes) and there was one treatment failure where treatment had been substantially delayed. The Thai patient was treated as part of a prospective, uncontrolled, observational study of 34 bleeding episodes in 22 patients in the Asia-Pacific region. Treatment was judged ineffective after 24 h, but full haemostatic control was subsequently achieved with intermittent rFVIIa therapy.

Adult↗
PubMed1990

Can the course of high dose cotrimoxazole for Pneumocystis carinii pneumonia in AIDS be shorter? A possible solution to the problem of cotrimoxazole toxicity.

Fifty consecutive patients with confirmed PCP received a high dose of cotrimoxazole for 14 d, or until development of intolerance, directly followed by reduced dose maintenance therapy. Seven individuals died during the high dose course. Twenty (47%) of the 43 survivors showed toxicity reactions that necessitated dose reduction to maintenance level on average after 9.6 d. Thirteen of these 20 individuals tolerated the reduced dose, and seven did not. No further cases of toxicity were observed. In 43 survivors only one early relapse (day 17) was observed in a patient who had received full dose treatment for 14 d. We conclude (1) that extending high dose cotrimoxazole therapy beyond 2 weeks is usually unnecessary, provided that reduced dose maintenance therapy is given directly, and (2) that dose reduction on appearance of toxicity signs during the second week of treatment is safe and allows two-thirds of patients to be maintained on cotrimoxazole with satisfactory results.

Acquired Immunodeficiency Syndrome↗
PubMed1978

Dose-dependent reductions by naloxone of analgesia induced by cold-water stress.

Animals exposed to cold-water swims, rotation, or inexcapable shocks, display analgesia comparable to that of 10 mg/kg of morphine. The present study investigated whether a narcotic antagonist would eliminate analgesia induced by cold-water swims. In one group of 12 rats, naloxone at 0, 1, 5, 10 and 20 mg/kg was administered at weekly intervals immediately preceding forced cold-water swims (2 degrees C for 3.5 min) and alterations in flinch-jump thresholds were determined 30 min thereafter. In a second group of six rats, the effects of the same dose range of naloxone were determined upon normal flinch-jump thresholds. Naloxone dose-dependently attenuated the cold-water swim-induced analgesia up to a maximal reduction of 50% at 20 mg/kg. In contrast, all doses of naloxone had no effects upon normal flinch-jump thresholds. Since low doses of naloxone completely abolish morphine-induced analgesia, the present data suggest that the analgesia induced by stress is not identical to that of opiates.

Analgesia↗
PubMed2001

Treatment of the jaundiced patient with breast carcinoma: case report and alternate therapeutic strategies.

BACKGROUND: Breast carcinoma in the setting of liver metastases and jaundice raises a complex therapeutic dilemma. Not only is the prognosis poor but toxicity related to treatment can be unpredictable due to altered drug clearance. Guidelines built around dose reduction have been suggested but often do not address the varied presentations in clinical medicine. Bilirubin exceeding 5.0 mg% often is considered an absolute contraindication to the administration of chemotherapeutic agents dependent on hepatic metabolism. METHODS: A 55-year-old woman with metastatic breast carcinoma to the liver and hyperbilirubinemia was treated with sequential, empiric chemotherapy agents with the goal of preventing severe toxicity through dose reduction, avoidance of combination therapy, divided doses (weekly therapy), and selection of drugs less dependent on hepatic clearance. Several attempts did not yield a regimen with a successful response, but toxicity was minimal. Eventually, a successful schedule and dose of an agent cleared by liver metabolism was individualized for the patient. RESULTS: After eight cycles of low dose weekly doxorubicin chemotherapy, the patient's symptoms resolved, bilirubin level normalized, and performance status returned to baseline. The patient remained on treatment and was alive 12 months later. CONCLUSIONS: The authors propose that altering a drug schedule by dividing doses may minimize toxicity, maintain dose intensity, and represent an alternative strategy for the treatment of patients with hepatic impairment.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Effects of relaxation intervention in phase II cardiac rehabilitation: replication and extension.

OBJECTIVES: To examine the effects of progressive muscle relaxation and guided imagery on psychological and physiologic outcomes in adults with cardiovascular disease who were participating in a phase II cardiac rehabilitation program. To examine tension levels, practice patterns, and perceived helpfulness of the intervention reported by subjects. DESIGN: Prospective, quasi-experimental, with random group assignment within sites. Independent replication and extension of a study by Bohachik (1984). SETTING: Four midwestern hospital-based phase II cardiac rehabilitation programs. PATIENTS: Fifty patients who within the preceding 12 weeks had had acute myocardial infarction or coronary artery bypass surgery or both, studied during 6 weeks of participation in a phase II cardiac rehabilitation program. OUTCOME MEASURES: Psychological measures included state and trait anxiety scores on the State-Trait Anxiety Inventory and reported symptoms on the Symptom Checklist-90-Revised. Physiologic measures were resting heart rate and blood pressure. Subjective tension levels before and after home practice, practice patterns, and perceived helpfulness of the intervention were examined. INTERVENTION: Individual instruction session in progressive muscle relaxation and guided imagery at the phase II cardiac rehabilitation program, followed by daily home practice with audiotape instructions over a 6-week period. RESULTS: No statistical differences at the p < or = 0.05 level were found in state anxiety scores or reported symptoms at study exit. However, reductions in mean subscale scores for interpersonal sensitivity (t [19] = 2.11, p < or = 0.05) and depression (t [19] = 2.07, p < or = 0.05) by paired t tests were found for the relaxation group (RG). The two groups differed at study exit in resting heart rate (t [42] = -2.02, p < or = 0.05) by independent t tests and in systolic blood pressure (F [1,42] = 5.13, p < or = 0.05) by analysis of covariance. The RG had a mean resting heart rate 8.6 beats/min lower than that of the control group (CG) and also had within-group reductions in mean heart rate (t [19] = 2.09, p < or = 0.05) by paired t tests. Contrary to expectation, the CG had a 3.5 mm Hg lower mean systolic blood pressure and within-group reductions in systolic (t [22] = 3.02, p < 0.01) and diastolic (t [22] = 3.83, p < 0.01) blood pressure by paired t tests. CG subjects had a greater number of dose increases in cardiac medications and fewer dose reductions than did RG subjects, who also had a higher number of dose reductions. RG subjects reported frequent practice of the technique, rated it as helpful, and reported lower subjective tension levels after practice. CONCLUSIONS: Findings in this study did not support those of Bohachik (who reported lowered state anxiety and fewer somatization, interpersonal sensitivity, and depression symptoms). More instruction sessions on the relaxation method may have resulted in more positive outcomes. However, the within-group scores for interpersonal sensitivity and depression, the reduction in heart rate, and the receptivity of subjects to this intervention suggest that it may be a feasible and helpful adjunctive therapy for participants in a phase II cardiac rehabilitation program.

Adult↗
PubMed2002

Isoflurane dosage for equivalent intraoperative electroencephalographic suppression in patients with and without epidural blockade.

UNLABELLED: We conducted a prospective, randomized, controlled trial to establish the effect of epidural blockade on isoflurane requirements for equivalent intraoperative electroencephalographic (EEG) suppression. Fifty patients undergoing abdominal hysterectomy received combined epidural and general anesthesia or general anesthesia alone with isoflurane and alfentanil. Isoflurane was administered by computer-controlled closed-loop feedback to maintain an EEG 95% spectral edge frequency of 17.5 Hz, a target chosen on the basis of a pilot study. In epidural patients, end-tidal isoflurane concentration (FE'(ISO)) was 0.19% smaller (95% confidence interval [CI], -0.32% to -0.06%; P < 0.01), mean arterial blood pressure was 17 mm Hg lower (95% CI, -24 to -9 mm Hg; P < 0.0001), and body temperature was 0.4 degrees C lower (95% CI, -0.7 to 0 degrees C; P < 0.05) than in controls. EEG bispectral index (BIS) was 4 points higher (95% CI, 1 to 7; P < 0.05). EEG median frequency and heart rate were similar in both groups. Epidural patients were 76% more likely (95% CI, 58% to 94%; P < 0.001) to require metaraminol for hypotension and were 28% more likely (95% CI, 3% to 53%; P < 0.05) to require glycopyrrolate for bradycardia. After surgery, the time to eye opening in epidural patients was 2.3 min shorter (95% CI, -4.2 to -0.5 min; P < 0.05). Time to eye opening correlated better with FE'(ISO) in the last 30 s of anesthesia (FE'(ISO) = 0.07 x time to eye opening + 0.31; r(2) = 0.59; P < 0.0001) than with BIS from the same period (BIS = 64 - 1.25 x time to eye opening; r(2) = 0.22; P < 0.001) (P < 0.0001). To maintain similar intraoperative spectral edge frequency, patients receiving combined epidural and general anesthesia require 21% less isoflurane than those receiving general anesthesia alone. This smaller isoflurane dose is associated with faster emergence from anesthesia. IMPLICATIONS: The dose of general anesthetic required to maintain similar intraoperative suppression of brain electrical activity is 21% less in patients with nerve blockade than in those without. This dose reduction results in faster waking times in patients with nerve blockade, which may reflect lighter intraoperative anesthesia. The dose of general anesthetic required to maintain similar intraoperative suppression of brain electrical activity is 21% less in patients with nerve blockade than in those without. This dose reduction results in faster waking times in patients with nerve blockade, which may reflect lighter intraoperative anesthesia.

Adult↗
PubMed1997

An analysis of the outcomes of treatment of small cell lung cancer in the elderly.

BACKGROUND: Many cases of small cell lung cancer will occur in the elderly population but optimal management of the disease in this age group remains uncertain. AIMS: To evaluate treatment of small cell lung cancer in the elderly in Australia and to compare treatment received and outcomes with those of younger patients. To draw insights from these observations into the optimal management of small cell lung cancer in the elderly. METHODS: A retrospective review of treatment charts and case notes for 51 elderly patients and 102 younger patients was undertaken. RESULTS: Elderly patients had similar baseline parameters with respect to disease stage and performance status. Elderly patients were mostly treated uniformly with combination chemotherapy, but suffered more dose reductions than younger patients. Benefits of chemotherapy were seen even in patients with poor performance status. Despite the dose reductions, response rates and survival times for elderly patients were usually similar to younger patients. CONCLUSIONS: Combination chemotherapy is beneficial to elderly patients with small cell lung cancer. Optimal therapy for the elderly may be different from that for younger patients and should be defined through prospective randomised clinical trials.

Age Factors↗
PubMed2007

16-MDCT angiography in living kidney donors at various tube potentials: impact on image quality and radiation dose.

OBJECTIVE: The objective of our study was to compare the performance of 16-MDCT angiography at various peak kilovoltage (kVp) settings and the impact of the different settings on image quality and on radiation dose in adult kidney donors. MATERIALS AND METHODS: Sixty-two renal donors (32 men, 30 women) who underwent 16-MDCT were divided into three groups: 18 subjects were studied at 140 kVp (group A); 20, at 120 kVp (group B); and 24, at 100 kVp (group C). Other constant scanning parameters were as follows: detector collimation, 0.625 mm; table feed, 9.375 mm/rotation; gantry rotation time, 500 milliseconds; and automatic current tube modulation (ATCM) using a noise index of 15. A total of 135-140 mL of iodinated contrast material (300 mg I/mL) was administered at 5 mL/s via an 18-gauge cannula, and arterial phase scanning was initiated using a bolus-tracking technique. Two observers evaluated image quality of the axial and 3D images and the visibility of branch order in the superior mesenteric artery (SMA) and renal arteries. Attenuation (in Hounsfield units [H]) in the aorta, SMA, and main renal artery was also measured by placing a region of interest. Radiation dose measurements were based on the scanner-generated CT dose index volume (CTDI(vol)). Each parameter tested was compared among the three groups using a nonparametric analysis of variance test, and a p value of 0.05 was considered significant. RESULTS: Differences in the quality of the axial images existed between groups A and C (p < 0.001) and between groups B and C (p < 0.01); the image quality of the 3D images and the visibility of branch order in the SMA and renal arteries were comparable for all groups. The difference in mean attenuation of the aorta, SMA, and renal arteries was significant between groups A and C (p < 0.001) and between groups B and C (p < 0.01). All groups had 100% diagnostic accuracy in identifying the number of renal arteries on the side of nephrectomy. The mean radiation dose in CTDI(vol) was 25 +/- 3 mGy at 140 kVp, 17 +/- 4 mGy at 120 kVp, and 12 +/- 3 mGy at 100 kVp (p < 0.001). CONCLUSION: Our initial observations suggest that the image quality of 16-MDCT angiography performed at 120 kVp is similar to that of CT angiography (CTA) performed at 140 kVp in adult kidney donors but with a significant radiation dose reduction. CTA at 100 kVp results in higher image noise but provides diagnostically acceptable images with significant radiation dose reduction compared with CTA at 120 or 140 kVp.

Adult↗
PubMed1999

Docetaxel: standard recommended dose of 100 mg/m(2) is effective but not feasible for some metastatic breast cancer patients heavily pretreated with chemotherapy-A phase II single-center study.

PURPOSE: Patients with metastatic breast cancer, especially those with progression after several prior chemotherapy treatments, need efficient chemotherapy. This study investigates the efficacy and toxicity of docetaxel in metastatic breast cancer patients with previous chemotherapy for metastatic disease. PATIENTS AND METHODS: Thirty-one women (median age, 52 years; range, 40 to 65 years) treated for metastatic breast cancer with docetaxel were included. Eleven patients had one metastatic site, 10 patients had two, and 10 patients had three or more. The planned dose of docetaxel per course was the standard treatment of 100 mg/m(2) (or 75 mg/m(2) if liver enzyme levels were abnormal) every 3 weeks, given for six or eight cycles. RESULTS: The overall response rate was 48% (three complete responses [CR] and 11 partial responses [PR] ), and the median duration of response was 7 months (range, 2 to 16 months). Twenty patients (65%) experienced fatigue, and 27 patients (87%) had alopecia. Fifteen cases (48%) of grade 4 leukopenia were observed. Edema with a weight gain of 2 to 15 kg was seen in 12 patients (39%), and mucositis occurred in 20 patients (65%). Twenty-three patients (74%) interrupted treatment before reaching the planned number of courses, nine patients owing to progression of cancer and 14 owing to toxicity. Dose reduction was required in 18 (61%) of the patients. Only two patients were able to receive the planned eight courses without dose reduction. CONCLUSION: Docetaxel is highly active in metastatic breast cancer, even as a third-line treatment, and can be considered as an efficient standard option in second-line treatment. The standard recommended dose level of 100 mg/m(2) is not feasible in heavily pretreated patients; therefore, for such patients, an initial dose level not exceeding 75 mg/m(2) is recommended.

Adult↗
PubMed1998

Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells.

An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.

Anticarcinogenic Agents↗
PubMed2000

Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma.

PURPOSE: The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas. METHODS: Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion. RESULTS: The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed müllerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%; P = 0.019). Three patients required dose reduction secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All significant toxicity was eliminated with dose reduction. CONCLUSIONS: Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS.

Adult↗
PubMed2006

Malignant lymphomas in the elderly: a single institute experience highlights future directions.

In this study, our experience with the diagnostics and treatment of malignant lymphoma patients were analyzed, with a special consideration of the elderly. Between 1980 and 2005, there were 181 cases found (35%) among 517 non-Hodgkin's lymphoma (NHL) patients and 46 cases (8.1%) among 565 Hodgkin's lymphoma (HL) patients, who were at least 65 years old at the time of diagnosis. Comparing elderly patients to young ones, the time from first symptoms to diagnosis was significantly longer (NHL: 7.6 months versus 4.1 months, HL: 11.4 months versus 5.6 months). B-cell and indolent NHL-s were more common (92.8% versus 79.2% and 56.4% versus 35.1%) such as classical lymphocyte predominant (cLP) HL-s (30.4% versus 15.0%); however nodular sclerosis (NS) HL-s occurred less frequently (10.9% versus 32.2%). Stages were more advanced and comorbidity was more common. Primary therapies were more often inappropriate (NHL: 20.4% versus 5.1%, HL: 26.0% versus 6.0%); there were more complications, but less cases with complete remission (NHL: 17.1% versus 61.1%, HL: 63.0% versus 79.2%) and dose reductions were more commonly applied (NHL: 46.7% versus 17.2%, HL: 52.9% versus 11.3%). Remission rates were significantly worsened by dose reductions (NHL: 68.5% versus 34.5%, HL: 61.8% versus 44.4%). Appropriate therapies resulted in significantly better overall survival (OS) rates (log-rank<0.05). It can be concluded that more favourable results can be achieved in the remission and survival rates of elderly malignant lymphoma patients if the appropriate curative or palliative therapies, considering new and less toxic protocols such as supportive care, are chosen.

Adolescent↗
PubMed2005

Center experience in liver transplantation (LTX): management of dermal side effects caused by sirolimus.

INTRODUCTION: Sirolimus improves post transplant maintenance therapy in LTX. Dermal side effects causing pain and discomfort can limit patients' compliance. The package insert mentions such skin disorders as acne and rash. One case of sirolimus-induced leucocytoclastic vasculitis is reported in the literature. METHODS: From July 1998 to October 2003, Sirolimus was implemented in the immunosuppressive protocol in 23 out of 60 liver recipients. Sirolimus target levels are between 3 and <10 ng/dl. Combination with a calcineurinblocker and/or MMF (mycophenolate mofetil) depending on liver function and creatinine is standard. Weekly patient monitoring in the first month after discharge included physical examination, blood samples and immunosuppresant trough levels. Biopsies were taken from untypical efflorescences. RESULTS: Three patients with non-specific effloresces were reported: one with leucocytoclastic vasculitis and one with exfoliate forearm dermatitis required change of medication while one perivascular lymphocytic eosinophilic dermatitis subsided after dose reduction. In three cases of mouth ulcer, trough levels exceeded 10 ng/dl and in six patients acne diminished after dose reduction. Eighteen out of 23 patients are still receiving sirolimus. Reasons for removal from the study were incompliance and incompatibility. Two patients died. DISCUSSION: Immunosuppressants inevitably produce side effects in TX recipients. The positive management of troublesome side effects contributes importantly to compliance and patient survival.

Acne Vulgaris↗
PubMed2004

A phase II study of irinotecan alternated with a weekly schedule of oxaliplatin, high-dose leucovorin and 48-hour infusion 5-fluorouracil in patients with advanced colorectal cancer.

OBJECTIVES: To evaluate the safety and efficacy of irinotecan (CPT-11) alternated with a weekly treatment for 4 weeks of oxaliplatin (L-OHP), high-dose leucovorin (LV) and a 48-hour 5-fluorouracil infusion (5-FU 48 h) as first-line chemotherapy for patients with advanced colorectal cancer (ACC). PATIENTS AND METHODS: Previously untreated patients with ACC received chemotherapy consisting of a weekly treatment for 4 weeks of L-OHP (65 mg/m2), high-dose LV (150 mg/m2) followed by a 5-FU 48 h infusion (2,300 or 1,800 mg/m2) alternated with CPT-11 (350 mg/m2). A cycle was to be performed every 8 weeks. Treatment was continued up to tolerance, disease progression or patient refusal. Forty consecutive patients with measurable ACC, aged 26-70, performance status < or =2, entered our study. RESULTS: Six complete and 17 partial responses were observed (overall response rate, 57.5%; 95% confidence interval, CI: 38.8-71.1%); an additional 35% of the patients had stable disease. The median duration of response was 10.9 months (range, 6.5-30+ months). The median time to progression and the median overall survival time were 11.4 (95% CI: 10.4-12.3) and 20.3 (95% CI: 16.4-23.7) months, respectively. At the median follow-up period of 24 months, 17 patients (42.5%) are still alive. After a median number of 4 cycles, one toxic death occurred. The incidence of grade 3-4 toxicity per patient in any cycle was: stomatitis 7.5%, nausea/vomiting 2.5% and diarrhea 45% for the infusional part, neutropenia 37.5%, anemia 2.5%, thrombocytopenia 5%, alopecia 5% and diarrhea 10% for the CPT-11 part of the regimen. Gastrointestinal toxicity was different according to the dose of 5-FU. Serious adverse events occurred most frequently when 5-FU was given at a dose of 2,300 mg/m2 with a high incidence of grade 3-4 diarrhea (72.2%) and stomatitis (16.6%), and led to dose reduction of 5-FU in 13 of 18 patients (72.2%). For 22 patients who started 5-FU at a dose of 1,800 mg/m2, a dose reduction of 5-FU was necessary only 5 times (22.7%). No patient discontinued treatment because of severe neurotoxicity. CONCLUSIONS: The activity of our alternating regimen of L-OHP/LV/5-FU 48 h and CPT-11 for not previously treated ACC patients is counterbalanced by a high toxicity and a inconvenient schedule.

Adult↗