Chemotherapeutic and targeted biological agents for metastatic bladder cancer: a comprehensive review.

The American Cancer Society estimates that 73 510 new cases of bladder cancer will be diagnosed and 15 000 deaths will result this year. The paper summarizes the clinical evidence for the use of platinum-based, non-platinum-based and new targeted biological agents, while reporting the future directions in the treatment of metastatic bladder cancer. For cisplatin-base regimens, the combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) has been the mainstream treatment for both advanced and metastatic bladder cancers. It showed significant improvement in the complete response rate and overall survival time in comparison with single-agent cisplatin. For cisplatin-ineligible patients, namely patients with renal impairment, symptomatic cardiac disease and poor performance status, alternative therapies consisting of paclitaxel, gemcitabine and carboplatin were shown to be of benefit. Pemetrexed and vinflunine have also shown effectiveness, with small but demonstrable overall survival benefits. Gemcitabine-based doublet therapies (combined with paclitaxel, docetaxel, irinotecan, oxaliplatin or epirubicin) have all been shown to be effective and well-tolerated. Several new targeted therapies, such as gefetinib, sorafenib and lapatinib, have received attention in recent years; however, their effectiveness as single agents in a relapse setting have not been optimal and more studies are warranted.

Testicular lymphoma: an update for clinicians.

Testicular lymphoma is a lethal disease with a median survival of approximately 12 to 24 months. It is the most common testicular malignancy in men older than 60 years of age. Testicular lymphoma has a predilection for widespread dissemination to unusual sites, including the central nervous system, contralateral testis, Waldeyer's ring, skin, and lung. Doxorubicin based chemotherapy with prophylactic intrathecal chemotherapy and radiation to the contralateral testis seems most promising. This review article will focus on the presentation, pathology, patterns of relapse and challenges in improving the outcome of this disease.

Multidisciplinary Cancer Care Model: A Positive Association Between Oncology Nurse Navigation and Improved Outcomes for Patients With Cancer.

BACKGROUND: Patients with cancer often experience prominent deficiencies in cancer care in the immediate period following initial cancer diagnosis. OBJECTIVES: This article aims to determine whether the inclusion of a gastrointestinal (GI) oncology nurse navigator (ONN) on the multidisciplinary cancer care team is associated with improved quality of care for patients. METHODS: This retrospective study compared randomly selected patients with GI cancer with and without an ONN. Two endpoints, the time from diagnosis to treatment and the average number of missed appointments, were evaluated through a review of healthcare records using the Epic electronic health records system. FINDINGS: Patients with an ONN had a shorter time lapse between diagnosis and treatment commencement (p < 0.001). In this group, the average time spent between initial diagnosis and the start of treatment was 15.15 days, compared to 42.93 days for patients who were not part of the multidisciplinary cancer care model.

A rare case of clear cell adenocarcinoma of the bladder with unique pathological features.

Clear cell adenocarcinomas of the urinary bladder are rare tumors with an unknown histogenesis. Since these tumors appear histologically similar to clear cell tumors of the female genital tract, a mullerian histogenesis has been proposed. Several publications have examined the immunohistochemical properties of clear cell adenocarcinomas to improve understanding of the cause and pathogenesis of this tumor. While specific criteria for a diagnosis of clear cell adenocarcinoma have not been defined, there are consistent staining patterns suggested for characterization. We present an important case of clear cell adenocarcinoma of the bladder with a unique staining pattern. We review the literature and discuss the differential diagnosis and various theories concerning the origin of this rare tumor.

Use of low molecular weight heparin and aminocaproic acid in chronic DIC associated with prostate cancer--a case report.

Disseminated Intravascular Coagulopathy (DIC) is the most common coagulopathy in patients with prostate cancer. Though rare, it could be fatal without treatment. Literature suggests that there is significant activation of fibrinolytic pathway. Pathophysiology of DIC in patients with prostate cancer is not completely understood. We present here a case of chronic DIC in a patient with metastatic androgen independent prostate cancer. His DIC was managed successfully with a combination of aminocaproic acid and low weight molecular heparin. The use of low molecular weight heparin may make management of chronic DIC in prostate cancer more feasible in an out patient setting.

Sacral epithelioid angiosarcoma associated with a bleeding diathesis and spinal epidural hematoma: case report.

Epithelioid angiosarcoma of bone is a rare, high-grade lesion that is highly vascular and can be associated with a bleeding diathesis. An association has been reported in angiosarcomas in other locations with coagulopathy from tumor-related disseminated intravascular coagulopathy and fibrinolysis. The authors report the case of a rare occurrence of a primary sacral epithelioid angiosarcoma associated with a large epidural hematoma and a severe bleeding diathesis. A 25-year-old woman presented with weakness, fatigue, neck and low-back pain, and progressive left S-1 radiculopathy. Imaging studies revealed a large ventral epidural hematoma extending from the sacral region rostrally to C-2 and a vascular tumor located in the sacrum. The patient underwent a sacral laminectomy, complicated by postoperative bleeding from the wound, and required massive transfusions. Ultimately, multimodal therapy was required to obtain hemostasis, including the use of endovascular embolization, radiation therapy, and an infusion of epsilon-aminocaproic acid with heparin. This case represents the first report of a primary epithelioid angiosarcoma in the sacrum and emphasizes that the coagulopathy seen in angiosarcoma is also a feature of this epithelioid variant.

Primary mediastinal large B-cell lymphoma in an HIV-infected patient.

HIV-related non-Hodgkin lymphoma is well documented in the literature. We report a case of an HIV-infected patient who presents with primary mediastinal large B-cell lymphoma. On review of the literature, this appears to be the first documented case of this subtype of large B-cell non-Hodgkin lymphoma seen in an HIV-infected patient. Our patient received CHOP (cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone) chemotherapy with granulocyte colony-stimulating factor support but unfortunately died a few days later.

Secondary hormonal manipulations in the management of advanced prostate cancer.

Prostate cancer is a heterogeneous disease and clinical outcomes vary considerably after failure of primary androgen ablation. With the development of new therapeutics the management of patients with androgen independent prostate cancer has changed considerably over the last few years. Multiple secondary hormonal manipulations are available and may lead to prolonged periods of clinical response. These maneuvers include the use of oral antiandrogens, antiandrogen withdrawal, ketoconazole, aminoglutethimide, corticosteroids and use of estrogenic compounds. This article reviews the clinical activity of these agents in management of patients with advanced prostate cancer.

Long-term complications of chemotherapy for germ cell tumours.

Testicular cancer is the most common solid tumour among young males aged 15-35 years. Cisplatin-based combination chemotherapy has changed the outlook of this disease. Disseminated testicular cancer, once uniformly fatal, now has a cure rate of more than 80% with combination chemotherapy. Systematic randomised trials have shown that cisplatin, etoposide and bleomycin (PEB) combination chemotherapy remains the mainstay of treatment. While there is a high cure rate with chemotherapy in patients with this disease, some long-term complications from chemotherapy have now been recognised, including secondary leukaemia, therapy-related solid tumours, nephrotoxicity, neurotoxicity, pulmonary toxicity, vascular toxicity and infertility. Etoposide, a DNA topoisomerase II inhibitor, is a significant risk factor for developing leukaemia; the risk appears to be correlated with the total dose given. Patients receiving cisplatin-based combination chemotherapy for testicular cancer also appear to have a higher relative risk for developing second non-germ cell malignancies; the greatest risks for therapy-related solid tumours were seen with a combination of radiation therapy plus chemotherapy. Long-term vascular toxicities associated with chemotherapy include Raynaud's phenomenon, acute myocardial infarction and cerebrovascular events. Bleomycin is thought to be the most important drug in the pathogenesis of Raynaud's phenomenon, while cisplatin is the most likely agent involved in myocardial infarction. Peripheral neuropathy is the most common form of neurotoxicity observed with cisplatin-based chemotherapy. Risk factors for the development of neural damage include a high cumulative dose of cisplatin, the use of vinblastine and the concomitant development of Raynaud's phenomenon. Cisplatin is also well known to cause significant nephrotoxicity. Approximately 25% of patients present with azoospermia after undergoing combination chemotherapy with a follow up of 2-5 years. Physician awareness of complications associated with chemotherapy is vital to maximise efficacy, minimise toxicity, and preserve quality of life after treatment. Sperm cryopreservation should be considered for patients who desire children. Close monitoring during therapy allows for the early diagnosis of complications, and close follow up of patients after the completion of therapy is necessary to monitor for relapse and development of long-term complications such as myelodysplastic syndrome and leukaemia. Despite these complications, given the potential for cure rates in this young group of patients, the benefits far outweigh the risks.

The evolving role of cytoreductive surgery for metastatic renal cell carcinoma.

Metastatic renal cell carcinoma is a devastating disease associated with poor survival. Immunotherapy is the mainstay of treatment, but response rates are low. The role of cytoreductive surgery in the presence of metastatic disease is evolving. From both retrospective and recently published randomized clinical trials, it is now apparent that among patients with metastatic renal cell carcinoma and good performance status, cytoreductive surgery followed by immunotherapy improves survival. However, this approach is likely to be detrimental in patients with poor performance status. Clinical trials of novel agents remain a priority in this disease.

Transitional cell carcinoma of the bladder producing parathyroid hormone-related protein (PTHrP).

Hypercalcemia associated with transitional cell carcinoma (TCC) is rarely encountered. We report a case of TCC of bladder with documented production of parathyroid hormone related protein (PTHrP). Our patient had a rapidly progressive course and died 2 months after radical cystectomy. Literature suggests that these patients present with advanced stage and carry a poor prognosis. The histopathologic features, treatment and prognosis associated with this rare paraneoplastic syndrome are reviewed.

Isolated late recurrence of renal cell carcinoma in the inferior vena cava.

The occurrence of an isolated late recurrence of renal cell carcinoma within the inferior vena cava (IVC) is a rare event. We present a case of a 55-year-old patient with recurrence in the IVC more than 3 years following her initial nephrectomy. The asymptomatic presentation of this patient with recurrent disease emphasizes the importance of close, long-term surveillance.

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer.

BACKGROUND: The objectives of the current study were to evaluate the safety and efficacy of gemcitabine and irinotecan (Irinogem) in patients with metastatic bladder cancer. Irinotecan and gemcitabine are newer-generation chemotherapeutic agents with different mechanisms of action, nonoverlapping toxicity profiles, and synergistic activity in vitro. METHODS: Sixteen patients have been enrolled, of which 13 are evaluable for response. The median age is 68.5 years (range, 52 to 82 y). According to the Bajorin prognostic model for metastatic bladder cancer, 8 patients were classified as "low risk" and 8 as "intermediate risk." Gemcitabine 1000 mg/m and irinotecan 100 mg/m were administered on days 1 and 8 of each 3-week cycle. All patients had histologically proven transitional cell cancer of the bladder with bidimensionally measurable disease. All but 2 patients were chemotherapy naive at enrollment. RESULTS: The median number of cycles administered was 4. Among the 13 patients evaluable for efficacy, objective radiographic response was documented in 8 patients (2 complete and 6 partial responses), 4 had stable disease, and 1 progressed on therapy. Median progression-free survival was 8.78 months (95% confidence interval, 5.98-15.38) and median overall survival was 13.51 months (95% confidence interval, 8.02-21.93). Toxicity evaluated in all 16 patients was modest: 2 episodes of febrile neutropenia, grades 3 to 4 neutropenia in 4 patients, grades 3 to 4 diarrhea in 2 patients, grades 3 to 4 fatigue in 1 patient, grades 3 to 4 nausea/vomiting in 2 patients, grades 3 to 4 neurological toxicity in 1 patient, and no grades 3 to 4 thrombocytopenia. No toxic deaths were noted. One patient discontinued therapy due to grade 4 fatigue, 1 due to stroke, 1 due to grade 4 colitis, 1 due to progressive disease, and 1 declined to participate in the trial after receiving the first cycle of therapy. CONCLUSIONS: The results of the current study suggested that the combination of Irinogem was an effective treatment for patients with metastatic bladder cancer, with manageable toxicities. The study was closed early due to delays in accrual and loss of funding. Hence, the study lacks adequate power to make definite conclusions. Further studies in multi-institutional setting in patients with normal and compromised renal function are warranted.

Phase 2 trial of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer.

PURPOSE: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). METHODS AND MATERIALS: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; "downstaged" patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. RESULTS: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. CONCLUSIONS: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.

Finasteride.

IMPORTANCE OF THE FIELD: Prostate cancer is the most common non-cutaneous malignancy in males in the US. Prostate cancer chemoprevention entails the use of agents which retard or inhibit the progression to invasive disease. Chemoprevention is an attractive option for patients with prostate cancer given the hormonally responsive nature of cancer, long latency period and high prevalence of the disease. AREAS COVERED IN THIS REVIEW: This review outlines a detailed background on the development of finasteride as a chemopreventive agent for prostate cancer. It discusses the Prostate Cancer Prevention Trial, a large randomized clinical trial that showed reduction in prostate cancer prevalence through the use of finasteride. In addition, an in-depth discussion involving theories on a higher incidence of high-grade cancer in the finasteride arm is presented. Other notable recently completed randomized trials and novel chemopreventive agents for prostate cancer are discussed as well. WHAT THE READER WILL GAIN: Readers will get an in-depth understanding of the balance of risks and benefits of finasteride for prevention of prostate cancer. TAKE HOME MESSAGE: Finasteride was the first 5alpha-reductase inhibitor to show a benefit in reducing prevalence of prostate cancer. It is well tolerated but a higher incidence of high-grade prostate cancer in men taking finasteride has hindered its use in clinical practice. It may temporarily shrink tumors that have a low potential for being lethal and is not approved as a chemopreventive agent.

Primary testicular lymphoma and AIDS.

Immunosuppressed patients have an increased risk for developing extranodal lymphoma, including testicular lymphoma. In AIDS patients, primary testicular lymphoma has been reported as an initial manifestation of the disease. These patients typically present at an early age; their lymphomas usually have aggressive histologic appearance and are associated with poor prognosis. We report a testicular lymphoma consistent with diffuse large B-cell lymphoma (DLBCL) in an AIDS patient and we review the literature on primary testicular lymphoma in AIDS patients.

Toxicity and survival outcomes of hyperfractionated split-course reirradiation and daily concurrent chemotherapy in locoregionally recurrent, previously irradiated head and neck cancers.

BACKGROUND: : Reirradiation of locoregionally recurrent, previously irradiated head/neck cancer may be considered in situations of unresectability, medical inoperability, or adverse pathologic features found at salvage resection. METHODS: : Retrospective cohort analysis of toxicity and survival outcomes in locoregionally recurrent, previously irradiated patients with head/neck cancer treated with hyperfractionated split-course radiotherapy and concurrent chemotherapy. RESULTS: : Between March 1998 and September 2006, 39 patients initiated reirradiation at median of 2.3 years (range, 0.5-19) following prior radiotherapy. At median survivor follow-up of 24.5 months (range, 3-63.9), 10 patients are alive without evidence of disease. Median survival is 19.0 months, with estimated 1-, 2-, and 3-year overall survivals of 60.1%, 45.1%, and 22.7%, respectively. Locoregional failure was the predominant site of postreirradiation recurrence. Male sex, total radiotherapy dose, cycles of chemotherapy completed, and clinical response were associated with improved overall survival. CONCLUSIONS: : Reirradiation can offer long-term survival for patients with recurrent, previously irradiated head/neck cancers.

Cold agglutinin induced autoimmune hemolytic anemia and NK-cell leukemia: a new association.

Cold agglutinin induced autoimmune hemolytic anemia is uncommonly associated with leukemia and lymphomas. We present a case of a young Mexican female presenting with a cold agglutinin hemolytic anemia with expression of a rare Pr antigen specificity and an aggressive NK-cell leukemia. Our patient had a rapid fatal course. To our knowledge this is the first reported case of such an association.

Locally advanced leiomyosarcoma of the urinary bladder: near-complete pathologic response to neoadjuvant gemcitabine and docetaxel.

Leiomyosarcoma of the urinary bladder is a rare mesenchymal tumor with distinct pathologic features. Although radical cystectomy is the standard therapy for locally invasive disease, available literature appears to support the benefit of perioperative chemotherapy, similar to that seen with the more conventional urothelial malignancies. We report on a 77-year-old gentleman with locally advanced leiomyosarcoma of the bladder achieving a near-complete pathologic response to neoadjuvant chemotherapy with a unique regimen: gemcitabine and docetaxel. Further study of this anthracycline-sparing regimen is warranted.