Pharmacotherapy of gestational trophoblastic disease

Gestational trophoblastic neoplasms are the most responsive of all solid tumours to chemotherapy leading to an overall cure rate of > 90%. Nonmetastatic disease (FIGO Stage I) and low-risk metastatic disease (FIGO Stages II and III; WHO score < 7) can be treated with single-agent methotrexate or actinomycin D protocols resulting in a survival rate approaching 100%. Metastatic high-risk disease (FIGO Stage IV or WHO score > 7) should be treated with initial intensive multimodality therapy with combination chemotherapy, consisting of etoposide, high-dose methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) and adjuvant radiotherapy and surgery when indicated. Despite this aggressive approach, ～ 30% of patients with high-risk disease will fail initial therapy or relapse from remission. Salvage chemotherapy with drug regimens containing platinum agents and etoposide, usually in conjunction with bleomycin or ifosfamide, as well as surgical resection of sites of resistant disease, will ultimately result in a survival rate of 80 – 90% for metastatic high-risk disease.     

Treatment of gestational trophoblastic tumors

A brief discussion of the definition, etiology, epidemiology, classification, and prognosis of the gestational trophoblastic tumor (GTT) is presented. Current therapeutic options are summarized. GTTs arise from fetal tissues and can be divided into three histologic categories, hydatidiform mole, chorioadenoma destruens, and choriocarcinoma. Clinically, it is classified as nonmetastatic, metastatic-low risk, or metastatic-high risk. Diagnosis is based on clinical signs and symptoms, ultrasound and X-ray examinations, and the presence of elevated serum levels of the B-subunit of human chorionic gonadotropin (hCG). Primary therapy for hydatidiform mole is evacuation of the uterine contents. Prophylaxis for metastases with actinomycin D sometimes is performed, but generally is not recommended. For persistent disease that is classified as nonmetastatic or low-risk metastatic, a methotrexate-leucovorin rescue protocol is preferred, with actinomycin D used in patients who show resistance to the regimen. Standard therapy for high-risk metastatic disease involves triple agent therapy with methotrexate, actinomycin D, and chlorambucil, but toxicity is significant. Other alternatives include the modified Bagshawe protocol, a VBC (vinblastine, bleomycin, cisplatin) regimen, cisplatin in combination with vincristine and high-dose methotrexate, and VP16-213 (etoposide) in combination with other agents. Other treatment modalities include radiation and surgery. Use of the most appropriate therapies can maximize the survival of a patient with gestational trophoblastic disease.     

Therapy for osteosarcoma: where do we go from here?

Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. Current optimal treatment for osteosarcoma consists of multi-agent chemotherapy and aggressive surgical resection of all sites of disease involvement. The current national and international cooperative trial for patients with newly diagnosed osteosarcoma builds upon the backbone of cisplatin, doxorubicin, and methotrexate. This protocol is designed to clarify whether (i) the addition of ifosfamide and etoposide to postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a poor histologic response to 10 weeks of preoperative chemotherapy; and (ii) the addition of pegylated interferon-alpha-2b as maintenance therapy after postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a good histologic response to 10 weeks of preoperative chemotherapy. However, the optimal treatment strategy (or strategies) for patients with relapsed or metastatic disease has yet to be defined. This remains one of the persistent challenges in the treatment of osteosarcoma.Recent therapeutic advances have focused on circumventing chemotherapy resistance mechanisms, incorporation of non-classical agents into upfront therapy, targeting of the tumor micro-environment, and investigating the role of novel delivery mechanisms.In patients with localized disease the 5-year survival rate is at least 70%; patients with metastatic or recurrent disease have <20% chance of long-term survival despite aggressive therapies. These figures have changed little in the past 2 decades. This review focuses on the current therapy for osteosarcoma, and highlights emerging strategies that will hopefully change the outlook for patients with this disease.     

Choriocarcinoma in a patient with human immunodeficiency virus: case presentation and review of the literature

A 26-year-old woman with choriocarcinoma and acquired immunodeficiency syndrome initially presented with hydatidiform mole and was treated with dilation and curettage. Because of persistent elevation of serum beta human chorionic gonadotropin, the patient was treated with combination chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMACO) for high-risk gestational trophoblastic tumor. The patient s initial stage was IIc. The serum beta human chorionic gonadotropin level returned to normal. Fourteen months later, the gonadotropin level again increased. The patient was treated with uterine curettage followed by vaginal hysterectomy. Despite further chemotherapy (with methotrexate and leucovorin, then oral etoposide), she died following metastasis of the tumor to the brain. Only four other cases of human immunodeficiency virus (HIV) infection with choriocarcinoma have been reported. There is no evidence to date that gestational trophoblastic disease is more prevalent in patients with acquired immunodeficiency syndrome. HIV infection and other immunodeficiency states, however, can influence the course of treatment and outcome in these patients. The low CD4 count in HIV infection may lead to a poor outcome despite chemotherapy.     

Multidisciplinary treatment for macrometastatic osteogenic sarcoma.

Using a co-ordinated multidisciplinary approach with surgery, radiation therapy, and chemotherapy, 14 out of 21 patients with metastases from osteogenic sarcoma were rendered free of disease for over two to over 18 months. Most patients had pulmonary metastases, two had bony metastases, and one had metastases in the iliac nodes. As part of this multidisciplinary approach weekly high-dose methotrexate was given and caused tumour regression in seven out of 15 patients. After all clinical evidence of disease had been removed high-dose methotrexate was administered every two to three weeks as maintenance treatment. To assess the efficacy of treatment the results were compared with those in a historical control group of 82 consecutive patients who developed pulmonary or other metastases. The results in the study group were significantly better. This experience may be similar to that in Wilms's tumour, where actinomycin D has increased the cure rate when administered as adjuvant therapy after treatment of localised or overt metastatic disease.     

The chemotherapy of head and neck cancer

Studies of combination therapy [with agents such as cisplatin, 5-fluorouracil (5-FU) and methotrexate] have shown some improvements in response rate; however, no obvious survival advantage over monotherapy in the treatment of patients with metastatic or advanced locoregional cancer of the head and neck have been observed. In the neoadjuvant setting, chemotherapy is helpful in preserving the larynx and hypopharynx but has no proven impact (positive or negative) on survival. New treatment options are needed to improve survival in head and neck cancer. Among the new options for chemotherapy in metastatic/recurrent disease is docetaxel. With monotherapy, response rates of 23-42% are seen, and, when used in combination with cisplatin and 5-FU, response rates of 52-100% have been reported in phase I/II trials. A phase III trial of the addition of docetaxel to standard neoadjuvant therapy with cisplatin and 5-FU is now underway.     

Pharmacotherapeutic treatment of germ cell tumors: standard of care and recent developments

Introduction: Testicular germ cell tumors are the most common malignancy among men aged 40 and less. Since the introduction of cisplatin-based combination chemotherapy, germ cell tumors are among the most curable solid tumors with cure rates of 95% in all patients and > 80% in metastatic disease.

Areas covered: Current standards and future developments in GCT treatment, including adjuvant chemotherapy, first line treatment for metastatic disease, and salvage regimens in case of relapse and refractory disease.

Expert opinion: Maintaining therapeutic success while further reducing treatment-related toxicity is paramount. Cancer-specific survival in localized disease approximates 100%. Therefore, orchidectomy followed by active surveillance is the preferred approach for all seminomas and non-seminomas lacking lymphovascular invasion. Non-seminomas with lymphovascular invasion should be offered adjuvant treatment with one cycle of bleomycin, etoposide and cisplatin (BEP). The BEP regimen remains standard of care for metastatic disease, while the role of primary high-dose chemotherapy in case of inadequate tumor-marker decline or presence of high-risk features (i.e. mediastinal origin, non-pulmonary visceral metastases) remains to be elucidated. Several curative salvage chemotherapy combinations are available, i.e. TIP, VeIP, GIP or high-dose carboplatin and etoposide. GOP is the current option of choice in cisplatin-refractory patients. Novel targeted agents failed to improve treatment outcome so far.     

A comparison of current neuroblastoma chemotherapeutics

Neuroblastoma is the most common solid tumour in childhood. Modern management includes a biopsy to perform genetic studies. Based on clinical data and Myc-N amplification (MNA), patients are divided in three prognostic groups: the low-risk (Stage 1, 2, 4S without MNA) has an event-free survival (EFS) of > 90% with surgery alone; the intermediate-risk (Stage 3, > 1 year of age, without MNA and Stage 3 and 4 infants without MNA) has an EFS of approximately 80% with mild chemotherapy and surgery; the high-risk group includes Stage 4, > 1 year of age and any stage and age with MNA. These patients are treated with chemotherapy, surgery, megatherapy, irradiation and 13-cis-retinoic acid. With this complex therapy, a 5-year EFS of 30-50% can be obtained.     

Diagnosis and treatment of patients with testicular germ cell cancer.

Testicular germ cell tumours are a highly curable malignancy even in the presence of metastases, with an overall survival rate of approximately 90 to 95% when all stages are considered. Current therapeutic strategies aim at risk-adapted therapy, trying to maintain favourable overall results while reducing treatment-related toxicity, particularly in non-advanced disease. In stage I disease, unilateral inguinal orchiectomy represents the standard diagnostic and therapeutic approach. For patients with clinical stage I seminoma, prophylactic para-aortic radiotherapy with 26Gy is commonly employed. In patients with nonseminomatous germ cell tumours (NSGCT) at clinical stage I, the 3 options are: (i) retroperitoneal lymphadenectomy; (ii) a wait-and-see strategy; or (iii) 2 cycles of adjuvant chemotherapy. The individual risk profile for tumour recurrence, mainly based on histopathological criteria such as vascular tumour invasion, should guide treatment decisions in this group of patients. Radiotherapy is still the standard approach in clinical stage IIA/B seminoma, whereas in patients with a low tumour burden of NSGCT, retroperitoneal lymphadenectomy is frequently used followed by surveillance or adjuvant chemotherapy. Primary chemotherapy in these stages of disease may be at least equally successful. Major progress has also been achieved in the treatment of NSGCT patients with metastatic disease greater than clinical stage IIB, for whom primary chemotherapy represents the standard approach. After cisplatin-based combination chemotherapy, between 70 and 90% of patients will achieve a durable remission. In patients with 'good risk' metastatic disease, 3 cycles of cisplatin, etoposide and bleomycin (PEB) remain the standard treatment, despite several randomised trials trying to avoid the lung-toxic bleomycin or substituting cisplatin by carboplatin. In patients with 'intermediate' and 'poor prognosis' disease, 4 cycles of PEB given at 3-week intervals are considered routine treatment. The role of high dose chemotherapy with peripheral autologous blood stem cell transplantation is currently being investigated for patients presenting initially with advanced (poor prognosis) metastatic disease and for patients with relapse after previous chemotherapy, in whom conventional-dose salvage regimens will only result in 20% long-term survival. Because of the large group of patients with metastatic disease being cured, the possible long-term adverse effects of treatment have become important. Only a slightly elevated risk for therapy-related secondary malignancies has been identified. Long-term adverse effects associated with cisplatin may affect a larger proportion of patients. Further research should focus on reducing the risk of chemotherapy-related chronic toxicity.     

Advances in the treatment of testicular cancer

Testicular cancer is the most common solid tumour in young men, and the treatment of testicular germ cell tumours (TGCT) has been called a success story of medical oncology, germ cell cancer being regarded as the "model of a curable neoplasm". Even with metastatic disease, high cure rates can be achieved: the overall 5-year survival for all stages of TGCT is approximately 80%. Today, elaborate systems for prognostic evaluation for gonadal and extragonadal germ cell tumours facilitate the choice of the most appropriate therapy for individual patients. In doing so, the ultimate goal of treatment is tumour-free survival for any patient with TGCT.This goal has already been reached for >99% of the patients with early-stage tumours, as well as for the majority of patients with advanced disease (56% of patients with metastases are considered to have a good prognosis at the time of diagnosis; the 5-year survival rate for this group is 90%). However, patients with 'intermediate' or 'poor' prognosis at the time of diagnosis, as well as patients with relapsed disease after cisplatin-containing therapy, still have an unsatisfactorily low 5-year survival rate after standard therapy with PEB (cisplatin, etoposide, bleomycin) of only 80%, 45-55% and 20-25%, respectively.Therefore, our goals must be (i) to limit acute and chronic toxicity by avoiding overtreatment for patients with localised disease and/or good prognosis with advanced disease; and (ii) to identify patients with poor prognosis and treat them in specialised centres, where not only is optimal interdisciplinary care available but new treatment strategies are being applied. For example, tandem high-dose chemotherapy regimens might be effective in achieving higher cure rates in these patients.     

长春新碱和甲氨蝶呤行口腔鳞癌术前新辅助化疗的临床研究

目的:观察长春新碱(vincristine)和甲氨蝶呤(methotrexate)新辅助化疗方案(VM方案)在口腔鳞状细胞癌治疗中的临床疗效.方法:对联合应用长春新碱和甲氨蝶呤行新辅助化疗的45例口腔鳞癌患者(辅助化疗组)和既往术前未作任何辅助治疗的50例口腔鳞癌患者(对照组)进行回顾性分析,辅助化疗组术前接受1个疗程的VM方案化疗后进行手术,术后两组接受同样治疗.统计辅助化疗组化疗疗效、术后肿瘤复发率、不良反应和生存质量评分,比较两组患者的术后肿瘤复发率和生存质量评分.结果:经1个疗程VM化疗方案治疗后,45例口腔鳞癌患者中临床部分缓解26例(57.8%),稳定19例(42.2%),化疗总有效率57.8%.VM方案不良反应小,不影响患者接受手术治疗.随访期间辅助化疗组出现肿瘤复发10例(22.2%)、肿瘤远处转移4例(8.9%),对照组出现复发21例(42.0%),转移14例(28.0%),组间比较差异有显著性.结论:术前应用长春新碱和甲氨蝶呤联合化疗在口腔鳞癌治疗中疗效显著,能提高患者生存质量.     

Multimodality therapy in surgically resectable early non-small cell lung cancer

Lung cancer is a global epidemic. Unfortunately only a fraction of patients can undergo curative surgery and in these, only one-third survive five years. The remainder die of locoregional and distant metastatic disease. With advances in chemotherapy for systemic control and radiation therapy for local control, responses and survivals have shown promise in extensive inoperable disease. In order to attempt to extend survival in extensive local but operable disease (Stage IIIa), these treatment modalities were added to the surgical regimen either before (neoadjuvant, induction) or after (adjuvant) surgery. Several small phase III trials substantiated the benefits. Since early lung cancer (Stage I and II) recur in 30% of instances to distant sites as well as regionally, multimodality therapies have recently been encouraged in global trials in an attempt to prolong time to recurrence and survival in this latter group of patients. A review follows:     

High-dose chemotherapy and stem cell support for breast cancer: where are we now?

To date, there is no definitive evidence that high-dose chemotherapy and haematopoietic stem cell support offers a survival advantage over conventional-dose chemotherapy for metastatic or high-risk primary breast cancer. Studies of metastatic disease discussed in this review have an adequate duration of follow-up given the short natural history of metastatic breast cancer. Thus, the results of these studies are unlikely to change with a longer observation period. On the other hand, studies of high-dose chemotherapy in the treatment of high-risk primary breast cancer need longer follow-up in light of the longer natural history of this type of disease. Results of unpublished studies and longer follow-up of available studies may still demonstrate a survival advantage for high-dose chemotherapy in patients with metastatic or high-risk primary breast cancer. We continue to encourage participation in innovative clinical studies.     

Neoadjuvant chemotherapy of breast cancer

About 80% of patients with breast cancer ultimately die of metastatic disease at 20 years. Distant metastases are more important as a cause of death than local or regional relapses. It is for this reason that adjuvant chemotherapy is necessary, especially in young patients and those with extensive disease. Initial chemotherapy preceding any local or regional treatment is justified on the grounds that both surgery and anaesthesia lead to immunodepression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials by Nissen-Meyer, Bonadonna and Cooper (1-3). In the present study 145 patients, including 67 with inflammatory breast cancer (IBC), were treated with 4-6 weeks of Velbe, thiotepa, methotrexate, fluorouracil and prednisone, with Adriblastin added for patients with IBC, T greater than 7 cm, or N2, N3. Because of tumour regression of greater than 50% observed in 80% of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium), resulting in complete remission in all these cases. Maintenance treatment with the same drugs was prescribed for 6-18 months depending on the initial stage. Tumour regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest being 42 months. Overall survival at 2 years for IBC is 90%, with a disease-free survival of 80%. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.     

Optimal drug therapy in the treatment of testicular cancer.

Although testes cancer is the most common malignancy affecting young men, dramatic survival rates are now possible with the development of optimal individualised drug therapy. Human chorionic gonadotropin and alpha-fetoprotein are important tumour markers associated with testes cancer, and can provide essential information about prognosis and treatment efficacy. For treatment purposes, testicular germ-cell malignancies are broadly classified as seminomatous or non-seminomatous. Early stage seminomas are treated with radiotherapy, while more advanced disease requires systemic chemotherapy. Stage I nonseminoma patients can now be offered the option of retroperitoneal lymph node dissection (RPLND) or close clinical observation, while patients with stage II or III nonseminoma should generally be treated with chemotherapy. The dramatic survival rates now apparent with chemotherapy are due in large part to the introduction of cisplatin (cisplatinum II)-based chemotherapy and to the optimisation of therapy based on pretreatment risk analysis. The most common chemotherapeutic regimen for standard risk patients includes cisplatin and etoposide (VP 16213) and long term disease-free survival rates exceed 80%. A subset of poor risk patients with significantly reduced survival can be defined. These patients, and patients with relapsed or refractory disease, should receive more aggressive regimens, and ifosfamide (isophosphamide) is proving to be a particularly promising new agent in this regard. High-dose carboplatin with autologous bone marrow rescue is another encouraging alternative currently being investigated for these patients. Chemotherapy, despite substantial effectiveness, is not without toxicity, which consists primarily of myelosuppression, nausea and emesis, and renal toxicity. With careful monitoring and prophylaxis, however, these toxicities can generally be ameliorated or avoided.     

Multisystem Langerhans cell histiocytosis in children: current treatment and future directions

Langerhans cell histiocytosis (LCH) is a rare (about 3-5 cases per million children aged 0-14 years), non-malignant disease characterized by proliferation and accumulation of clonal dendritic cells, extreme clinical heterogeneity, and an unpredictable course. Three large-scale, international, prospective therapeutic studies (LCH-I to III) for multisystem LCH (MS-LCH) have been conducted by the Histiocyte Society since 1991. The cumulative lessons from these studies are summarized in this review. Patients with MS-LCH represent a heterogeneous group with respect to disease severity and outcome, therefore treatment stratification and risk-tailored treatment are mandatory. The risk for mortality can be predicted based on involvement of 'risk organs' (e.g. hematopoietic system, liver, and/or spleen) at diagnosis and on response to initial therapy (assessed after 6-12 weeks of treatment). Thus, patients without involvement of risk organs (low-risk group) are not at risk for mortality but need systemic therapy in order to control the disease activity and avoid reactivations and permanent consequences. Patients with risk organ involvement (risk group) are at risk for mortality, and lack of therapy response defines a subgroup with a particularly dismal prognosis (high-risk group). Those patients in the risk group who respond to therapy and survive are at risk for reactivations and permanent consequences. The LCH-I study compared the efficacy of vinblastine and etoposide, and concluded that they are equivalent single-agent treatments for children with MS-LCH. However, the results of this trial were inferior with respect to response rate at week 6, disease reactivation rate, and sequelae, when compared with historical trials using more intensive regimens. The combination of prednisolone and vinblastine was established as a standard first-line treatment through the LCH-II and LCH-III studies. The regimen consists of one to two 6-week courses (continuous oral corticosteroids 40?mg/m2/day for 4 weeks, tapered over 2 weeks plus weekly vinblastine intravenous push) of initial therapy, followed by a continuation phase (three weekly pulses of oral prednisolone 40?mg/m2/day for 5 days plus a vinblastine injection). The addition of a third drug to the standard combination (etoposide in LCH-II and methotrexate in LCH-III) failed to significantly improve survival in the risk group. The remaining mortality in the risk group is about 20%, and up to 40% in the high-risk group. Concerning low-risk MS-LCH, comparison of results of the LCH-II study with historical data suggested that the remaining reactivation rate of about 50% (and possibly permanent consequences) could be reduced by prolongation of the total treatment duration. To study this hypothesis, in the low-risk group of the LCH-III study standard maintenance therapy was randomly given for a total treatment duration of 6 and 12 months. Unpublished preliminary data from this recently closed trial suggested that prolongation of the treatment duration may significantly improve reactivation-free survival. In summary, several studies have shown that systemic therapy is indicated for all patients with MS-LCH. A standard two-drug regimen consisting of an initial 'intensive' phase for 6-12 weeks, followed by a less intensive 'maintenance phase' for a total treatment duration of at least 12 months is recommended for patients treated outside of clinical trials. Non-responders, particularly those with progressive disease in risk organs, are eligible for experimental salvage approaches. Remaining questions will be addressed in the upcoming LCH-IV trial, which is in the process of intensive preparation.     

Selection of candidates for oral etoposide salvage chemotherapy in heavily pretreated breast cancer patients

Metastatic breast cancer (MBC) is still in most cases an uncurable disease and the main goal of treatment is a good quality of life for these patients. Therefore it is very important to select patients who are appropriate candidates for the particular salvage chemotherapy (CT) schedule. The aim of our study was to assess treatment response to oral etoposide, and to analyze its relationship with patients' and disease characteristics. Seventy-five patients with bidimensionally measurable MBC were included into our study. For most of the patients treatment with etoposide was third-line CT regimen and most of them (90%) had been exposed to previous anthracycline-based CT. Etoposide was administered orally at a dose of 100 mg/day for 10 days every 3 weeks. The overall response rate was 37% (95% CI: 27-50%) with a median time to progression (TTP) and survival of 4.5 and 12 months, respectively. Patients with a long disease-free interval, predominant soft tissue and bone metastases, and less than three metastatic sites responded better to oral etoposide; however, a significantly better response was achieved only in those who had responded to previous CT (46 versus 19%, p=0.04), especially to anthracyclines (50 versus 17%, p=0.016). Response to previous anthracycline-based regimen was the only characteristic that significantly influenced TTP (median TTP: 7 versus 2.5 months, p=0.0066) and survival (median survival: 13.8 versus 5 months, p=0.0072). Toxic side effects were generally mild. Salvage CT with oral etoposide is an appropriate treatment for patients who respond to previous CT, particularly to anthracyclines. It combines a favorable toxicity profile with the major advantage of an oral drug administered at home.     

Comparative tolerability of chemotherapy regimens for germ cell cancer.

Germ cell tumours, even at an advanced stage, represent a unique model of malignant curable disease since >80% of patients are expected to be cured after appropriate therapy: surgery and radiotherapy in early stages, and chemotherapy and surgery in advanced stages. In advanced stages, serum tumour marker levels as well as extrapulmonary (brain, liver and bone) visceral metastases are the most important prognostic factors that affect treatment modalities. 'Gold standard' regimens for germ cell cancer currently include etoposide plus cisplatin with (BEP) or without (EP) bleomycin. In patients with good risk disease (90% cure rate), the optimal regimen of chemotherapy should combine the best efficacy and the least toxicity. As a result of randomised trials, 3 regimens can be currently recommended: (i) 4 cycles of EP; (ii) 4 cycles of BEP (with etoposide 350 mg/m2 per cycle); or (iii) 3 cycles of BEP (with etoposide 500 mg/m2 per cycle). In patients with poor risk disease, 4 cycles of BEP (with etoposide 500 mg/m2 per cycle) allow a disappointing cure rate of 50%. The long term toxicity of these regimens (gonadal toxicity and secondary malignancies) appears to be negligible and clearly does not challenge current standard strategies.     

Treatment of platinum-resistant ovarian cancer

In the United States, almost 70% of the 23,000 women diagnosed annually with epithelial ovarian cancer present with advanced disease (FIGO stages III-IV). Primary therapy for these patients includes surgical cytoreduction and 6-8 courses of platinum- and taxane-based chemotherapy. Although 90% of patients will respond to this multi-modality combination regimen, most patients will experience recurrences. The 5 year survival for women with stage III disease is 15-30% and 0-20% for those with stage IV disease. Medical and gynecological oncologists, therefore, must be prepared to treat many women with recurrent ovarian cancer.     

A Review of Immune Checkpoint Inhibitors for the Management of Locally Advanced or Metastatic Urothelial Carcinoma

Urothelial carcinoma (UC) is the second most common malignancy of the genitourinary system and the sixth most common cancer in the United States. The overall incidence of UC appears to be on the decline, but death rates have remained stable. Stage IV metastatic disease is associated with only a 5% survival rate at 5 years. Gemcitabine and cisplatin combinations or dose‐dense methotrexate, vinblastine, doxorubicin, and cisplatin are the preferred regimens for individuals with advance, metastatic disease and a good performance status and organ function. Second‐line therapies in this setting are limited. During the course of 1 year, five immune checkpoint inhibitors were approved for treatment of cancers in the locally advanced or metastatic setting: atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Immunotherapies have played a significant role in the treatment of various cancers and have continued to expand. It is of utmost importance that practitioners include checkpoint inhibitors as treatment options for UC. Based on the limited data, pembrolizumab and atezolizumab may be the drugs of choice, as they are supported by the most influential data to date; however, further research is warranted. Ongoing clinical trials will further assess the benefits of inducing cellular immunity in the treatment of UC. These therapies mark a new landscape in the treatment of UC. In this article, the available data on immune checkpoint inhibitors for the treatment of locally advanced or metastatic UC and their place in therapy are reviewed.