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Background: Urothelial carcinoma of the upper urinary tract (UUT-UC) was a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. High-risk patients had poor outcomes. Because of the rarity of these tumors, randomized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable. Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high-risk, postsurgical UUT-UC patients., Methods: Using a multi-institutional, international retrospective database, identified were 627 patients with high risk UUT-UCs (pT3N0, pT4N0 and/or N+ and/or M+) who underwent surgical removal. Only patients who received adjuvant chemotherapy were included., Results: Overall, 140 patients (22.6%) with a median age of 67 years were included. The median follow-up was 22.5 months. The 5-year, overall survival for the entire cohort was 43%, the 5-year recurrence-free survival was 54%, and metastasis-free survival was 53% at 5 years. Positive surgical margins were an independent prognostic factor for recurrence (P = .06), cancer-specific mortality (P = .05), and overall mortality (P = .02) of any cause. Adjuvant chemotherapy was not linked with overall or cancer-specific survival in patients with high risk disease (adjuvant chemotherapy [n = 140] vs no treatment [n = 487]) (P >.5)., Conclusions: Adjuvant postoperative chemotherapy did not offer any significant benefit to overall survival in our population. Additional data were necessary, and studies enrolling patients at high risk in clinical trials investigating neoadjuvant chemotherapy in conjunction with chemotherapy should have been highly encouraged., (Copyright © 2011 American Cancer Society.)

Physicians who are responsible for the delivery of systemic treatment in lung cancer should be aware of the potential risk of drug-induced pulmonary toxicity (DIPT), because such toxicity may develop in the context of a multifactorial clinical condition. First, most patients with lung cancer may suffer from other non-neoplastic, smoking-related lung diseases, such as emphysema and chronic obstructive lung disease, which may generate pathologic changes in lung parenchyma. In addition, lung cancer itself may worsen the respiratory function, inducing atelectasis and lymphangitic carcinomatosis. The superimposed iatrogenic damage may lead to respiratory failure and, sometimes, death. The risk of DIPT from chemotherapeutic agents has been widely examined in the past; and, currently, the potential for lung toxicity has been extended by the introduction of molecular targeted therapies. Because there are no univocal criteria with which to recognize DIPT, the diagnosis often is made by exclusion; consequently, it is hard to establish an early diagnosis. The objective of this review was to describe the major DIPTs associated with antineoplastic agents against nonsmall cell lung cancer to help physicians with this difficult diagnostic challenge., (Copyright © 2011 American Cancer Society.)

The proteasome is responsible for the degradation of intracellular proteins, including several involved in cell cycle control and the regulation of apoptosis. Preclinical studies have shown that the proteasome inhibitor bortezomib decreases proliferation, induces apoptosis, enhances the activity of chemotherapy and radiation, and reverses chemoresistance in a variety of hematologic and solid malignancy models in vitro and in vivo. Proteasome inhibition with bortezomib has specifically promoted apoptosis of tumor cells through the stabilization of p53, p21, p27, Bax, and IkappaBalpha, resulting in nuclear factor kappaB inhibition. Bortezomib was the first proteasome inhibitor to enter clinical trials. In two Phase II trials, SUMMIT and CREST, it was found that treatment with bortezomib, alone or in combination with dexamethasone, produced durable responses with meaningful survival benefits in patients with recurrent and/or refractory multiple myeloma. In the APEX Phase III trial, bortezomib produced significant survival benefits and improved response rates over high-dose dexamethasone at first recurrence and beyond in patients with multiple myeloma. Clinical trials evaluating the safety and activity of bortezomib alone or in combination regimens with dexamethasone, doxorubicin, melphalan, prednisone, and/or thalidomide in the treatment of patients with newly diagnosed multiple myeloma have shown encouraging results. Preliminary studies suggest that bortezomib may serve as induction therapy before stem cell transplantation. Proteasome inhibition with bortezomib also has shown activity with manageable toxicity in mantle cell and other lymphomas, leukemias, and solid malignancies, including nonsmall cell lung carcinoma. Further studies with bortezomib as monotherapy and in combination regimens in the treatment of solid and hematologic malignancies are warranted., ((c) 2005 American Cancer Society.)

Background: This study addressed the question of whether limited surgery for primary malignant melanoma with a 2-cm margin is as good as a 5-cm margin. An update of a 16-year follow-up is provided., Methods: Nine European Centers, over a period of 5 years, prospectively randomized 337 patients with melanoma measuring less than 2.1 mm in thickness to undergo a local excision with either a 2-cm or a 5-cm margin. Three hundred twenty-six patients were eligible for statistical analysis. Excluded from the trial were patients older than 70 years; those with melanomas from the toe, nail, or finger; and those with acral-lentiginous melanoma. A separate randomization was performed to independently test an adjuvant treatment with a nonspecific immunostimulant, isoprinosine, compared with observation. The median follow-up time was 192 months (16 years) for the estimation of survival and disease recurrences., Results: There were 22 tumor recurrences in the 2-cm arm and 33 in the 5-cm arm. The median time to disease recurrence was 43 months and 37.6 months, respectively. The 10-year disease-free survival rates were 85% for the group with a 2-cm margin and 83% for the group with a 5-cm margin. There was no difference in the 10-year overall survival rates (87% vs. 86%). Isoprinosine did not demonstrate any activity in this setting., Conclusions: The authors concluded that for melanoma less than 2.1-mm thick, a margin of excision of 2 cm is sufficient. A larger margin of 5 cm does not appear to have any impact on either the rate or the time to disease recurrence or on survival., (Copyright 2003 American Cancer Society.)

Background: Quality-of-life (QoL) issues have become increasingly important as the number of newly diagnosed patients with cancer increases and survival improves. In 1983, Coates et al. reported a survey of patient perceptions of the side effects of cancer chemotherapy and showed the importance of including patient feedback for the accurate assessment of QoL (Eur J Cancer Clin Oncol. 1983;19:203-208.). The authors carried out a similar survey in 100 patients with cancer with the objectives of 1) investigating the changes in patient perceptions that have occurred and 2) evaluating the impact of new treatments on the profile of chemotherapy side effects among patients receiving anticancer drugs., Methods: One hundred patients attending the outpatient Medical Oncology Department of the Pitié Salpêtrière Hospital Group were surveyed between August 1998 and February 2000 by trained interviewers who were blinded to the patients' treatment. Patients identified all side effects associated with their treatment using a set of 45 cards that named physical side effects (Group A) and a set of 27 cards that named nonphysical side effects (Group B), and the patients ranked these side effects according to severity. The top 5 cards from each group were then combined, and the resulting 10 cards were rated again by severity, regardless of group. Results were analyzed for the entire cohort and for demographic, social, and clinical subgroups., Results: The participants included 65 women and 35 men; the most common malignancies were breast carcinoma (40 patients), gastrointestinal carcinoma (19 patients), lung carcinoma (7 patients), and ovarian carcinoma (9 patients). Patients rated affects my family or partner as the most severe side effect, alopecia was second, and fatigue was the third most severe. Effects on work or home responsibilities, effects on social activities, and loss of interest in sex were ranked fourth, fifth, and sixth, respectively. The results contrasted with those of Coates et al., in which affects my family or partner was ranked 10th, and fatigue was ranked 8th., Conclusions: Patient perceptions of the side effects of cancer chemotherapy have changed markedly. In the current study, fatigue and psychosocial QoL concerns predominated, compared with emesis, nausea, and negative reactions to the treatment visit in the original survey. The current findings are consistent with the progress that has been made in reducing certain chemotherapy-associated toxicities. Fatigue, however, although it often is related to anemia and is treatable with recombinant human erythropoietin, remains a major concern. The emotional, social, and sexual consequences of cancer treatment present continuing challenges in efforts to optimize QoL and to develop effective supportive care., (Copyright 2002 American Cancer Society.)

Background: In this study, the authors identified seven-year survivors after completion of the French multicenter Phase II trial of fotemustine for the treatment of metastatic malignant melanoma., Methods: One hundred sixty-nine patients with metastatic malignant melanoma were included in this Phase II study. One hundred fifty-three patient records were evaluable with an overall response rate of 24.2%., Results: Five of these patients are alive and in complete remission. One patient had a complete response after fotemustine administration and then relapsed. One patient had a partial response. Three patients had stable disease. These five patients underwent surgery for relapse or residual disease and subsequently achieved durable complete remission., Conclusions: Long term survival may be the outcome after surgical resection of residual metastatic melanoma after chemotherapy.

A sandwich enzyme-linked immunosorbent assay was developed to assess Fc-gamma receptor III (Fc gamma RIII), based on a combination of two non-competing monoclonal antibodies. This receptor was detectable in the serum of eight out of 23 patients with primary Sjögren's syndrome and two out of 23 normal controls. The proportion of Fc gamma RIII-carrying polymorphonuclear (PMN) cells was lower (P < 0.05) in the patients with cell-free Fc gamma RIII (90.4 +/- 7.5%) than in the remainder (84.8 +/- 8.3%). The PMN cell functions were evaluated and the diminished adherence (71.7, geometric mean) and chemotaxis (1.23) paralleled the Fc gamma RIII release. The relative inefficiency of PMN cells in SS might be due to phagocytosis of immune complexes.

One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.

This article describes four cases of non-Hodgkin's lymphomas occurring after successful treatment of Hodgkin's disease (HD). The clinical symptoms consisted of digestive disorders, and the histology confirmed an intestinal involvement in these four patients. In all cases patients had diffuse large cell types (intermediate or high grade). The respective role of HD treatment (combination chemotherapy in 3 of 4 patients with irradiation in 3 of 4 patients) and of other pathogenic hypotheses, are discussed.