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Background: Magnetic resonance imaging (MRI) has been a useful technique for the assessment of patients with multiple myeloma (MM). We evaluated the prognostic significance of different MRI patterns in symptomatic patients with MM. Patients and methods: A total of 142 symptomatic MM patients underwent MRI before treatment. MRI patterns of involvement were correlated with known prognostic variables, including the International Staging System (ISS), response to treatment and survival. Results: Focal marrow lesions were identified in 50% of patients, diffuse marrow replacement in 28%, a variegated pattern in 14% and normal pattern in 8%. When patients with the diffuse pattern were compared with patients with the other MRI patterns, they had features of more advanced disease such as higher ISS, anemia, hypercalcemia, elevated lactate dehydrogenase and extensive marrow plasmacytosis. Response rate was similar among patients with different MRI patterns. Median survival was 24 months for patients with the diffuse pattern, 51 months for those with the focal pattern, 52 months for those with the variegated pattern and 56 months for patients with the normal pattern (P = 0.001). The presence or absence of a diffuse MRI pattern separated patients with ISS stages I and II into two subgroups with significantly different survival times of 28 months and 61 months, respectively (P = 0.01). Furthermore, a diffuse MRI pattern predicted inferior outcome regardless of whether or not patients had received high-dose therapy with autologous stem cell transplantation. Conclusion: Diffuse marrow replacement on MRI adds to the evaluation of patients with multiple myeloma and their management.

Background The potential role of the adult thymus in T-cell homeostasis subsequent to lymphopenia remains the subject of debate. We examined whether thymic activity contributes to reconstitution of the peripheral T-cell pool, a critical process for patients recovering from antineoplastic therapy. Methods In selected patients with various neoplastic diseases we assessed peripheral blood lymphocyte subsets by flow-cytometry, including thymus-derived, CD4+ T cells expressing the CD45RA molecule, and thymic size rebound by CT scan before, and 3, 6 and 12 months after completion of cytotoxic therapy. Results Adult patients (n = 21, mean age of 30 years, range 18-49) had higher baseline numbers of B and lower numbers of NK cells than elderly patients (n = 15, mean age of 79 years, range 70-91), while total T-cell numbers did not differ. Despite the reduction of lymphocyte counts being comparable in the adult (mean of 45%) and elderly (mean of 49%) groups, occurring at, or near, completion of treatment, an enlargement of the previously atrophic thymus was evident in 63% of the adult, but in none of the elderly, subjects. In 22 patients who remained active disease-free during the following year, B cells and NK cells recovered to pretreatment levels as soon as at 3 months, whereas overall T-cell recovery occurred at 6 months post-treatment. Thymic rebound, observed in 11 of 22 patients who were of younger age, correlated significantly with a faster and more complete recovery of CD45RA+ CD4+ (mainly helper-naive) T cells. Conclusion The adult thymus appears capable of regeneration, at least up to middle age, contributing significantly to the reconstitution of the peripheral T-cell pool following chemotherapy-induced lymphopenia. In advanced age, however, although peripheral homeostatic pathways appear intact, regeneration of the naive repertoire is incomplete.

Background: The majority of patients with advanced urothelial cancer are elderly, but data regarding this specific age group are limited. We compared the tolerability and efficacy of first-line platinum (cisplatin or carboplatin)-based chemotherapy in elderly patients ( greater than or equal to70 years) with those in younger patients. Patients and methods: A total of 381 patients with advanced urothelial carcinoma received CIMV (cisplatin, ifosphamide, methotrexate, vinblastine) (n=32), MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) (n = 105), DC (docetaxel, cisplatin) (n = 174), CaG (carboplatin, gemcitabine) (n = 64) or other regimes (n = 6) and were included in this analysis. Results: A total of 116 patients were greater than or equal to70 years. Elderly patients experienced more frequent neutropenia grade 3/4 (55% versus 37%, P=0.087) and renal toxicity (28% versus 10%, P=0.033) among patients treated with CIMV/MVAC, and neutropenic infections (4% versus 0%, P=0.019) among patients treated with DC. Median survival did not differ significantly between elderly and younger patients (9.3 versus 10.5 months, P=0.16). Eastern Cooperative Oncology Group performance status (PS) and haemoglobin were independently associated with prognosis. Patients with PS <2 and haemoglobin greater than or equal to10g/dl had a median survival of 14 months as opposed to 5 months for patients with PS greater than or equal to2 or haernoglobin <10g/dl (P <0.001). Conclusion: Elderly patients with advanced urothelial cancer tolerate platinum-based chemotherapy well and derive the same benefit as their younger counterparts.

Objective. Patients with epithelial ovarian cancer (EOC) who relapse more than 6 months following completion of platinum-based primary chemotherapy are considered platinum-sensitive, and can be effectively retreated with cisplatin or carboplatin. The nucleoside analogue gemcitabine has proven activity in both platinum-sensitive and platinum-resistant disease. We conducted a phase II study using the combination of carboplatin and gemcitabine for the treatment of patients with relapsed platinum-sensitive and paclitaxel-pretreated EOC. Methods. Forty-three patients were treated with gemcitabine 1000 mg/m(2), intravenously, over 30 min on days 1 and 8, and carboplatin at AUC 5 on day 1. Courses were administered every 3 weeks on an outpatient basis. Results. Among 37 patients with measurable or evaluable disease, 15 (40.5%) achieved an objective response including 10 complete and 5 partial responses. The median overall survival was 24.5, months, and the median time to progression for all patients was 9 months. The treatment was well tolerated without toxic deaths; the most common toxicities were Grade 3 or 4 neutropenia, anemia, and thrombocytopenia that occurred in 69%, 26%, and 24% of patients, respectively. Conclusions. The combination of carboplatin and gemcitabine is a well-tolerated outpatient regimen with activity in patients with relapsed platinum-sensitive and paclitaxel-pretreated EOC. However, a randomized prospective study is justified to define whether the addition of gemcitabine to single-agent carboplatin results in improved efficacy in this subset of patients. (C) 2003 Elsevier Inc. All rights reserved.

Background: To compare survival between patients with advanced breast cancer (ABC) treated with epirubicin/paclitaxel (Taxol) or paclitaxel/carboplatin (Cp) chemotherapy. Patients and methods: From January 1999 to April 2002, 327 eligible patients with ABC were randomized to receive either paclitaxel 175 mg/m(2) in a 3-h infusion followed by epirubicin (EPI) 80 mg/m(2) (group A) or paclitaxel, as in group A, followed by Cp at an AUC of 6 mg x min/ml (group B) every 3 weeks for six cycles. Results: After a median follow-up of 23.5 months, median survival was not significantly different between the two groups (22.4 months versus 27.8 months, P=0.25), whereas median time to treatment failure was significantly longer in patients treated with paclitaxel/Cp (8.1 months in group A versus 10.8 months in group B, P=0.04). Both regimens were well tolerated. In total, 39 patients (24%) in group A and 46 (29%) in group B suffered at least one severe side-effect. Quality-of-life assessment and cost analysis did not reveal any significant differences between the two groups. Conclusion: Our study suggests that the paclitaxel/Cp combination is an effective therapeutic alternative for patients with ABC in which anthracycline administration has the potential of being harmful.

Background: Small series and retrospective studies have suggested that treatment with gemcitabine may be associated with pulmonary toxicity. However, a prospective evaluation of cancer patients treated with gemcitabine-based chemotherapy without neoplastic involvement of the thorax and without administration of radiotherapy has not been performed. Patients and methods: To investigate this issue, 41 consecutive patients receiving gemcitabine and carboplatin underwent prospective evaluation of lung function, which included pulmonary symptoms, pulmonary function tests, arterial blood gases and radiographic studies. Assessment was performed before and after completion of chemotherapy in all patients. Patients with a substantial decline in diffusion capacity for carbon monoxide (DLCO), defined as a drop of greater than or equal to20%, were reassessed 2 months later. Results: After chemotherapy, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, alveolar volume or total lung capacity. In contrast, there was a significant decline in DLCO (73 +/- 22 versus 67 +/- 24% predicted; P = 0.017) and in carbon monoxide transfer coefficient (KCO) (89 +/- 24 versus 80 +/- 24% predicted; P = 0.004). Arterial blood gases did not change following treatment. Ten of the 41 patients (24%) exhibited a substantial decline in DLCO, which, however, recovered within 2 months (DLCO at baseline, immediately after therapy and at 2 months after completion of treatment, 84 14, 58 16 and 77 +/- 17% predicted, respectively; P<0.001; baseline DLCO versus DLCO at 2 months, P>0.05). Four of the 41 patients (10%) experienced dyspnea, which was self-limiting, with the exception of one patient who developed interstitial lung fibrosis. Among the various risk factors examined, older age, female gender and lower baseline DLCO were associated with more profound changes in DLCO post-treatment. Conclusions: This prospective analysis show

Background: The purpose of this study was to evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (dMRI) in detecting bone marrow involvement in cancer patients. Patients and methods: We studied 50 consecutive patients with histologically confirmed malignant dissemination to the bone marrow, using dMRI of the lumbosacral spine. Time-signal intensity curves were generated from regions of interest (ROIs) obtained from areas of obvious bone marrow disease (group B). In 16 patients from group B with focal disease, ROIs were also placed on areas with apparently normal bone marrow on static magnetic resonance images (group C). Twenty-two patients with no history of malignancy were used as a control group (group A). Wash-in (WIN) and wash-out (WOUT) rates, time to peak (TTPK), time to maximum slope (TMSP) values and WIN/TMSP ratios were calculated for each patient. Mean values for the three groups were compared statistically. Six patients from group B had follow-up dMRI after chemotherapy: four patients achieved a clinical partial response and two had resistant disease. Results: A significant difference was found between groups A and B for all values. Between groups A and C, in spite of the similar static MRI appearance, all values were significantly different. Between groups B and C, a significant difference was found for WIN, WOUT rates and WIN/TMSP ratio. Follow-up dMRI data analysis correlated well with clinical staging. Conclusions: dMRI can distinguish normal from malignant bone marrow. It may identify malignant bone marrow infiltration in patients with negative static MRI and serve as both a diagnostic and prognostic tool for patients with bone marrow malignancies.

BACKGROUND. The combination of paclitaxel with a platinum analogue is the preferred chemotherapy regimen in the treatment of advanced epithelial ovarian carcinoma. The alkylating agent ifosfamide has shown activity in refractory or recurrent ovarian cancer. We conducted a Phase II study with the combination of ifosfamide, paclitaxel, and cisplatin for the treatment of newly diagnosed patients with advanced, suboptimally debulked ovarian carcinoma. METHODS. Thirty-five consecutive patients with advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage III or IV) and residual disease larger than 2 cm after staging laparotomy and cytoreductive surgery were treated with paclitaxel, 175 mg/m(2), as a 3-hour intravenous infusion on Day 1, cisplatin 75 mg/m2 intravenously over 2 hours on Day 2, and ifosfamide 1500 mg/m2 intravenously over I hour on Days 1-3 (with sodium 2-mercaptoethone sulfonate [MESNA] uroprotection). Courses were administered every 3 weeks on an outpatient basis. Granulocyte-colony stimulating factor was given at a dose of 5 mug/kg/day on Days 7-11. RESULTS. Among 26 patients with measurable disease, 22 (85%) achieved an objective response including 15 complete and 7 partial responses. With a minimum follow-up of 46 months, the median overall survival was 52.8 months (range, 5.3-56.6+ mos), whereas the median time to progression for all patients was 22.2 months. The median remission duration for women with measurable disease who responded to treatment was 12.6 months. The treatment was tolerated relatively well without toxic deaths; the most common toxicity was Grade 3 or 4 neutropenia that occurred in 42% of patients. Significant peripheral neuropathy (Grade 2 or higher) developed in 35% of patients. CONCLUSION. The combination of ifosfamide, paclitaxel, and cisplatin is a well-tolerated outpatient regimen with significant activity in the treatment of newly diagnosed FIGO Stage III or IV epithelial ovarian carcinoma

Purpose: To review the clinical features, complications, and treatment of Waldenstrom’s macroglobulinemia, a low-grade lymphoproliferative disorder that produces monoclonal immunoglobulin (Ig) M. Methods: A review of published reports was facilitated by the use of a MEDLINE computer search and by manual search of the Index Medicos. Results: The clinical manifestations associated with Waldenstrom’s macroglobulinemia can be classified according to those related to direct tumor infiltration, to the amount and specific properties of circulating IgM, and to the deposition of IgM in various tissues. Asymptomatic patients should be followed without treatment. For symptomatic patients, standard treatment consists primarily of oral chlorambucil; nucleoside analogs, such as fludarabine and cladribine, are effective in one third of previously treated patients and in up to 80% of previously untreated patients. Preliminary evidence suggests that anti-CD20 monoclonal antibody may be active in about 30% of previously treated patients and that high-dose therapy with autologous stem-cell rescue is effective in most patients, including some with resistance to nucleoside analogs. Conclusion: Waldenstrom’s macroglobulinemia has a wide clinical spectrum that practicing physicians need to recognize early to reach the correct diagnosis. When therapy is indicated, oral chlorambucil is the standard primary treatment, but cladribine or fludarabine can be used when a rapid cytoreduction is desirable. Prospective randomized trials are required to elucidate the impact of nucleoside analogs on patients’ survival. A nucleoside analog is the treatment of choice for patients who have been previously treated with an alkylating agent. (C) 2000 by American Society of Clinical Oncology.

BACKGROUND. The combination of paclitaxel with cisplatin or carboplatin has become the preferred chemotherapy regimen in the treatment of epithelial ovarian carcinoma. Anthracyclines also have activity in this disease. We conducted a Phase II study by using the combination of paclitaxel, cisplatin, and epirubicin for the treatment of advanced ovarian carcinoma. METHODS. Forty consecutive patients with optimally (n = 7) or suboptimally (n = 33) debulked advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV) were treated with paclitaxel, 135 mg/m(2), as a 3-hour intravenous infusion, cisplatin 75 mg/m(2) intravenously (i.v.), and epirubicin 50 mg/m(2) i.v. every 3 weeks on an outpatient basis. Granulocyte-colony stimulating factor was administered at a dose of 5 mu g/kg/day on Days 5-9. RESULTS, Among 28 patients with measurable disease, 24 (86%%) achieved an objective response including 19 complete and 5 partial responses. Among 18 patients who underwent reassessment laparotomy, pathologic complete response was confirmed in 9 patients. At a minimum follow-up of 40 months, the median overall survival had not been reached whereas the median time to progression for all patients was 18.7 months. The median remission duration for women with measurable disease who responded to treatment was 14 months. The treatment was well tolerated without toxic deaths; the most common toxicity was Grade 3/4 neutropenia that occurred in 30% of patients. Significant neuropathy (Grade 2 or higher) developed in only 8% of patients. CONCLUSIONS. The combination of paclitaxel, cisplatin, and epirubicin is a well tolerated outpatient regimen with significant activity in the treatment of advanced epithelial ovarian carcinoma. Cancer 2000;89:1547-54. (C) 2000 American Cancer Society.

Objectives, Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent carcinoma of the endometrium, and the combination of these two agents has shown activity in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent carcinoma of the endometrium to evaluate its activity and to define its toxicity. Methods, Twenty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m(2) administered intravenously over a 3-h period followed by cisplatin 75 mg/m(2) administered intravenously with granulocyte colony-stimulating factor (G-CSF) support. The chemotherapy was repeated every 3 weeks for a maximum of six courses, Results. Sixteen patients (67%; 95% confidence interval, 45-84%,) achieved an objective response, including seven complete responses and nine partial responses, The median duration of response was 7 months, and the median times to progression and survival for all patients were 8.4 and 17.6 months, respectively, Some degree of neurotoxicity occurred in 44% of patients. Grade 3 or 4 toxicity included granulocytopenia in 22% of patients and peripheral neuropathy in 9%. Conclusion. The combination of paclitaxel with cisplatin with G-CSF support appears active in patients with metastatic or recurrent carcinoma of the endometrium, The significant incidence of neurotoxicity is of concern and alternative methods of administration of the two agents could be evaluated. (C) 2000 Academic Press.

Granulosa cell tumour of the ovary is a rare neoplasm of low malignant potential, late recurrences, local spread and high survival rates. We report the MR imaging appearance of invasion of the liver parenchyma by recurrent granulosa cell tumour of the ovary 15 years after initial diagnosis. (C) 2000 Published by Elsevier Science ireland Ltd. All rights reserved.

Bone metastases from solid primary tumors, as well as multiple myeloma and secondary lymphoma may all present with bone lesions and associated soft-tissue masses on magnetic resonance images of the spine. Tn bone metastases and myeloma, the cortex of the affected bone is usually destroyed and a bulging contour is observed at the site of extraosseous spread. In cases of lymphomatous involvement of the bone marrow, however, we have observed that spread to the extraosseous soft-tissues occurs without alteration of the shape or contour of the affected bone. In order to assess whether this pattern of spread is indeed suggestive or even diagnostic of lymphoma of the bone marrow, we reviewed spinal bone marrow MR images of 66 patients, with bone metastases from solid primary tumors (33 patients), multiple myeloma (20 patients) and stage TV lymphoma with bone marrow involvement (13 patients), who had bone lesions and contiguous soft-tissue masses. If tumor was present on either side of the bony cortex but the contour of the affected bone was preserved, a “wrap-around” sign was diagnosed. A “wrap-around” sign was found in 12 of the 13 patients with lymphoma but in none of the patients with metastases or myeloma. On MR images of the bone marrow, the demonstration of tumor spread beyond the bony cortex without disruption of the outline of the diseased bone may favor the diagnosis of lymphoma more than that of metastases or multiple myeloma.

Purpose: Both docetaxel and cisplatin have moderate activity in patients with advanced urothelial cancer. We performed a multicenter phase II study in order to assess the efficacy and toxicity of the combination of these two agents in patients with advanced carcinoma of the urothelium. Patients and methods: Sixty-six patients not amenable to curative surgery or irradiation were enrolled onto this cooperative group study and treated on an outpatient basis with docetaxel 75 mg/m(2) followed by cisplatin 75 mg/m(2), both administered intravenously. Granulocyte-colony stimulating factor was administered subcutaneously at a dose of 5 mu g/kg daily from day 5 until resolution of neutropenia. The chemotherapy was administered every three weeks for a maximum of six courses in patients without evidence of progressive disease. Results: Thirty-four of sixty-six patients (52%, 95% confidence interval 40%-64%) demonstrated objective responses, with eight achieving clinical complete responses and twenty-six partial responses. A multivariate logistic regression analysis indicated that the patients most likely to respond were those without lung metastasis and without weight loss before treatment. The median duration of response was 6.1 months and the median times to progression and survival for all patients were 5 and 8 months, respectively. Absence of anemia, of liver metastases and of weight loss correlated with longer survival. Grade greater than or equal to 3 toxicities included granulocytopenia in 33% of patients, anemia in 14%, diarrhea in 13% and emesis in 7% of patients. Conclusion: The combination of docetaxel and cisplatin appeared relatively well tolerated and moderately active in patients with advanced urothelial cancer. The patients most likely to benefit were those without weight loss and without lung or liver metastases.