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.     

Pre-clinical activity of taxol in non-seminomatous germ cell tumor cell lines and nude mouse xenografts

Taxol (Paclitaxel) is a novel anti-cancer drug which has shown excellent clinical activity in a variety of solid tumors, particularly in metastatic breast and ovarian cancer. 70-80% of patients with metastatic non-seminomatous germ cell tumor (NSGCT) attain disease free status with standard cisplatin-based combination chemotherapy but the emergence of drug resistance still prevents a small proportion of these patients from achieving long-term remission. Here we report the results of pre-clinical studies investigating whether taxol exhibits cross-resistance to cisplatin or ifosfamide in human NSGCT cell lines and in a cisplatin refractory xenograft model of human NSGCT. Following 96h drug exposure in a 5-day sulphohodamine B (SRB) in vitro assay, taxol demonstrated potent cytotoxicity in cell lines which were cisplatin sensitive (577 LM, H32, H12.1; mean IC50s 1.5-3.0 nM) or those with acquired or intrinsic cisplatin resistance (H12DDP, H23; mean IC50s 2.5 nM). Compared to the drug sensitive cell line, H12.1, the IC50 values of taxol were increased in cell line 1777NRp Cl-A with intermediate level resistance to cisplatin and ifosfamide (4.7 nM; p > 0.05) and significantly elevated in cell line 1411HP, with a high level of cisplatin resistance (6.9 nM; p > 0.01). The latter 2 cell lines may represent models corresponding to patients relapsing after high-dose platinum-based chemotherapy who seem to be resistant to taxol therapy. The IC50s of taxol in H32 and H12DDP were approximately 100 fold lower following drug exposure times exceeding 24 hours compared with short exposure times (1-6h). Dose dependent anti-tumor activity was observed with taxol in a cisplatin-refractory xenograft model of NSGCT (H23), with significant anti-tumor activity observed at a dose of 15 mg/kg/d injected intra-venously on days 1 through 5. The results of this study are in accordance with the most recent clinical data which showed that taxol is a useful drug in relapsed or cisplatin-refractory testicular germ cell cancer, with significant anti-tumor activity being observed in 25% of patients, but poor activity in patients previously treated with high-dose therapy. Further pre-clinical research, especially using models such as 1411HP and 1777NRp Cl-A, on the combinations of taxol with other regimens are required to enable successful treatment of the most drug resistant relapsed germ cell tumors.     

Current pharmacotherapy for testicular germ cell cancer

Introduction: With the implementation of platinum-based chemotherapy, germ cell tumors (GCTs) became a model for a curable solid tumor, with survival rates of 95% in all patients with >80% survival in metastatic stages.

Areas covered: Herein, the authors review the current standards of adjuvant chemotherapy for stage I GCTs as well as first-line and salvage treatments for metastatic disease. Novel approaches for refractory disease are also reviewed.

Expert opinion: Active surveillance should be considered for all stage I patients and is the preferred approach for stage I seminoma. In stage I non-seminomas with vascular invasion, one cycle of bleomycin, etoposide, and cisplatin (BEP) substantially reduces the relapse risk. For most advanced GCTs, BEP remains the first-line standard of care. For poor prognosis disease treatment, stratification according to tumor marker decline is recommended. The role of primary high-dose chemotherapy (HDCT) for selected very high-risk patients remains to be prospectively evaluated. Salvage HDCT at relapse seems superior to conventional chemotherapy, retrospectively. The treatment of multiply relapsed disease remains challenging. The gemcitabine/oxaliplatin/paclitaxel (GOP) protocol is considered the standard for refractory disease. However, overall, outcomes are poor and new treatment approaches are urgently needed with targeted therapies so far failing to yield relevant clinical activity.     

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.     

Comparative activity of four anthracyclines against heterotransplanted germ cell tumor lines

Though the majority of patients with metastatic nonseminomatous germ cell tumors can be cured by modern combination chemotherapy, for those patients who do not respond to standard therapy additional drugs are needed. The activity of three new anthracycline derivatives, 4-epidoxorubicin, THP-doxorubicin and mitoxantrone against two established human testicular cancer cell lines in comparison to doxorubicin and to cisplatin, vinblastine, bleomycin and ifosfamide was studied in a xenograft model. All drugs were given at equitoxic doses. There were no differences in antitumor activity between the four anthracycline derivatives. In line H 12.1, which is very sensitive to the standard drugs cisplatin, vinblastine, bleomycin and ifosfamide, all four anthracycline derivatives were inferior to these agents. In contrast, in line H 23.1, where all four standard agents showed a significant lower antitumor activity when compared to line H 12.1, the anthracyclines preserved their activity, indicating a lack of cross resistance. Thus the anthracycline derivatives seem to be inferior to the standard drugs as first line treatment but because of apparent lack of cross resistance they deserve further evaluation in refractory germ cell tumors.     

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.     

Current treatment for ovarian cancer

Ovarian cancer is the most lethal gynaecologic malignancy. Epithelial ovarian cancer (EOC) constitutes approximately 90% of cases of ovarian cancer and 70% of the patients with EOC present in advanced stage. Treatment of EOC usually consists of cytoreductive surgery which includes total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy and lymphadenectomy followed by adjuvant chemotherapy. Current adjuvant chemotherapy includes paclitaxel and either cisplatin or carboplatin given every 3 weeks for six cycles. The combination paclitaxel and platinum chemotherapy achieves clinical response in approximately 80% of patients. However, most patients will have tumour recurrence within 3 years following treatment. Patients with platinum-sensitive tumours can be re-treated with platinum and/or paclitaxel. Those with platinum-resistant tumours have poor prognosis and treatment is palliative. Options of treatment in these patients include topotecan, doxil, gemcitabine, etoposide, or enrolment in clinical trials. Future research needs to focus on the role of cytoreductive surgery, second-look surgery, consolidation chemotherapy, development of new chemotherapeutic agents, chemoresistance modulators, as well as new approaches to the treatment of women with ovarian cancer.     

New prospects for the treatment of germ-cell tumours

Germ-cell tumours are rare tumours of testicular, ovarian and extra-gonadal origins. Most are curable by cisplatin-based chemotherapy regimens and surgery. Treatment strategy is based on risk factor assessment. The standard cytotoxic drugs used for the treatment of this disease are: etoposide, cisplatin, bleomycin and ifosfamide. More than 80% of patients are cured by standard treatment. There is a dose-response relationship for cisplatin, up to standard 33 mg/m2/week/dose-intensity. However, further dose escalation has failed to demonstrate an increased response. Carboplatin has been shown to be less active than cisplatin. Activity has been demonstrated with nitrogen mustard, actinomycin, mithramycin, vinblastine, methotrexate and recently with paclitaxel and gemcitabine. Activity is questionable with carboplatin, oxaliplatin, lobaplatin, mitomycin and anthracyclins. No activity has been reported with vindesine, vinorelbine, mitoxantrone, AMSA and topotecan. New treatment strategies are developed in poor-risk group patients and in patients who fail to achieve complete remission status or whom experience recurrent disease. Intensification of chemotherapy is one of the tested strategies. Consolidation high-dose chemotherapy with haematopoietic stem-cell support is under evaluation. Until now, no trial has proven its superiority over standard chemotherapy regimens. Other studies concern the role of repeated cycles of high-dose chemotherapy with haematological support. Innovative strategies consist of introducing new drugs or new schedules: paclitaxel in combination with either ifosfamide and cisplatin or epirubicin, short, recycled chemotherapy regimens, use of cisplatin non-cross-resistant drugs and different time infusion administration of drugs. The aim of these studies is to decrease the residual proportion of treatment failures in this highly curable disease, which constitutes a good model for clinical research in cancer chemotherapy.     

New prospects for the treatment of germ-cell tumours

Germ-cell tumours are rare tumours of testicular, ovarian and extra-gonadal origins. Most are curable by cisplatin-based chemotherapy regimens and surgery. Treatment strategy is based on risk factor assessment. The standard cytotoxic drugs used for the treatment of this disease are: etoposide, cisplatin, bleomycin and ifosfamide. More than 80% of patients are cured by standard treatment. There is a dose-response relationship for cisplatin, up to standard 33 mg/m²/week/dose-intensity. However, further dose escalation has failed to demonstrate an increased response. Carboplatin has been shown to be less active than cisplatin. Activity has been demonstrated with nitrogen mustard, actinomycin, mithramycin, vinblastine, methotrexate and recently with paclitaxel and gemcitabine. Activity is questionable with carboplatin, oxaliplatin, lobaplatin, mitomycin and anthracyclins. No activity has been reported with vindesine, vinorelbine, mitoxantrone, AMSA and topotecan. New treatment strategies are developed in poor-risk group patients and in patients who fail to achieve complete remission status or whom experience recurrent disease. Intensification of chemotherapy is one of the tested strategies. Consolidation high-dose chemotherapy with haematopoietic stem-cell support is under evaluation. Until now, no trial has proven its superiority over standard chemotherapy regimens. Other studies concern the role of repeated cycles of high-dose chemotherapy with haematological support. Innovative strategies consist of introducing new drugs or new schedules: paclitaxel in combination with either ifosfamide and cisplatin or epirubicin, short, recycled chemotherapy regimens, use of cisplatin non-cross-resistant drugs and different time infusion administration of drugs. The aim of these studies is to decrease the residual proportion of treatment failures in this highly curable disease, which constitutes a good model for clinical research in cancer chemotherapy.     

Systemic chemotherapy in the treatment of malignant melanoma

Different postsurgical therapies are used for the treatment of metastatic melanoma. This article reviews the use of chemotherapeutic agents in the treatment of patients with metastatic malignant melanoma. A variety of single chemotherapy agents have been evaluated, although the most widely used chemotherapeutic in the treatment of metastatic melanoma is dacarbazine. In order to improve the rate and duration of responses, combination chemotherapy was developed. The most common combined chemotherapy regimens used as standard for the treatment of metastatic melanoma are Dartmouth regimen, CVD (cisplatin + vinblastine + dacarbazine) and BOLD (bleomycin + vincristine + lomustine + dacarbazine). However, Phase III trials have failed to demonstrate a significant benefit in survival in patients treated with polychemotherapy compared to those treated with dacarbazine alone. The use of classical systemic chemotherapy still has a role in the treatment of patients with metastatic melanoma. Immunotherapy and biochemotherapy have no additional advantage over chemotherapy.     

Systemic chemotherapy in the treatment of malignant melanoma

Different postsurgical therapies are used for the treatment of metastatic melanoma. This article reviewes the use of chemotherapeutic agents in the treatment of patients with metastatic malignant melanoma. A variety of single chemotherapy agents have been evaluated, although the most widely used chemotherapeutic in the treatment of metastatic melanoma is dacarbazine. In order to improve the rate and duration of responses, combination chemotherapy was developed. The most common combined chemotherapy regimens used as standard for the treatment of metastatic melanoma are Dartmouth regimen, CVD (cisplatin + vinblastine + dacarbazine) and BOLD (bleomycin + vincristine + lomustine + dacarbazine). However, Phase III trials have failed to demonstrate a significant benefit in survival in patients treated with polychemotherapy compared to those treated with dacarbazine alone. The use of classical systemic chemotherapy still has a role in the treatment of patients with metastatic melanoma. Immunotherapy and biochemotherapy have no additional advantage over chemotherapy.     

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.     

Pharmacokinetic evaluation of gemcitabine hydrochloride for the treatment of cervical cancer

INTRODUCTION: Cervical cancer is the third most prevalent cancer in females worldwide. When advanced, the disease requires primary radiation concurrent with chemotherapy. However, chemotherapy alone is the standard treatment for recurrent/persistent/metastatic disease. AREAS COVERED: Areas covered in this review include the treatment of advanced cervical cancer with gemcitabine as radiosensitizer, either alone or in combination with cisplatin. The use of gemcitabine for recurrent/persistent/metastatic cervical cancer is also reviewed. EXPERT OPINION: Statistically significantly better survival rates are achieved with cisplatin doublets against cisplatin alone, in the management of recurrent/persistent/metastatic cervical cancer. The choice of the cisplatin doublet with paclitaxel, vinorelbine, gemcitabine and topotecan arms should be based on physician preference, pre-existing morbidity and patient-related factors. In advanced disease, a recently reported Phase III trial establishes the novel regimen of concurrent gemcitabine plus cisplatin and external radiation, followed by brachytherapy and two adjuvant 21-day cycles of gemcitabine plus cisplatin, as significantly improving survival outcomes when compared with the current standard of care. The increased acute toxicity of this regimen is clear; however, this should not deter its incorporation into clinical practice, in that the toxicity is predictable and manageable; nevertheless, the occurrence of late toxicity and survival at longer follow-up time are reasonable concerns in this regimen.     

Comparative cytotoxicity of oxaliplatin and cisplatin in non-seminomatous germ cell cancer cell lines

Approximately 70-80% of patients with metastatic testicular cancer will become disease free with cisplatin-based chemotherapy and most of these patients will be longterm survivors. Despite these impressive results, the two limitations of cisplatin are its severe and potentially long-term side-effects, and the emergence of drug resistance which prevents a small proportion of these patients from achieving long-term remission. Oxaliplatin has an improved toxicity profile compared to cisplatin and contains the diaminocyclohexane (DACH) substituent known to be correlated with a lack of cross resistance with cisplatin. A phase II study has shown interesting activity when used in combination with cisplatin in cisplatin-refractory testicular cancer patients. Here we report the results of the first in vitro study investigating whether oxaliplatin as a single agent exhibits cross-resistance to cisplatin in a panel of non-seminomatous germ cell tumor (NSGCT) cell lines using short and long-term drug exposures in a five-day sulfhodamine B in vitro cytotoxicity assay. Oxaliplatin cytotoxicity was significantly superior to cisplatin in cell lines with both acquired (H12DDP) and intrinsic (1777NR Cl-A) intermediate level resistance to cisplatin. Following 24h or 96h drug exposure the fold resistance in H12DDP and 1777NR Cl-A was 1.7-2.2 with oxaliplatin compared to 3.9-6.1 with cisplatin. The cytotoxic activity of oxaliplatin was not significantly different from that of cisplatin in cisplatin-senstive cell lines or in cell lines with a high level (10-20 fold) of cisplatin resistance. The results of this study suggest that further pre-clinical studies in NSGCT are of interest, particularly in combination with cisplatin, ifosfamide and etoposide. Furthermore, the in vitro results support the use of an oxaliplatin administration schedules giving prolonged drug exposure, such as the flat or circadian rhythm-modulated schedule already under investigation for oxaliplatin.     

宫颈癌分期治疗研究状态综述

目的探讨基于临床评估的宫颈癌分期对治疗选择的影响。方法复习近年来宫颈癌方面的研究文献,予以综述。结果微侵袭性宫颈癌可通过非根治性手段治愈。Ib~IIa期宫颈癌,根治性手术与根治性放疗效果相当,但存在并发症差异。术式选择需综合考虑分期及个体选择。根治性手术前的新辅助化疗可提高Ib期生存期。联合应用化、放疗为IIb~IVa期的新标准方法。结论针对个体化、宫颈癌分期、年龄、临床状态及肿瘤相关因素等的综合对策在宫颈癌治疗中疗效可靠。     

紫杉醇联合顺铂用于局部晚期宫颈癌24 例疗效观察

目的评价紫杉醇联合顺铂（TP）治疗对局部晚期宫颈癌的临床疗效。方法 2007年3月～2011年5月经病理确诊的24例Ib-IIIb期宫颈癌患者,采用TP方案化疗2个疗程后行广泛性子宫切除术及盆腔淋巴结清扫术。观察宫颈癌病灶、宫旁组织在化疗前、后的改变,化疗毒副反应以及术后病理情况等。结果化疗后,完全缓解3例（12.5%）,部分缓解16例（66.7%）,化疗有效率为79.2%（19/24）,且宫颈癌病灶、宫旁组织有不同程度的改善。化疗后21例患者进行了广泛性子宫切除术及盆腔淋巴结清扫术,手术切除率达到87.5%。结论术前紫杉醇联合顺铂化疗可提高宫颈癌的近期疗效,患者能较好耐受。     

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.     

术前动脉灌注化疗治疗局部晚期宫颈癌疗效分析

目的观察动脉灌注介入化疗对局部晚期宫颈癌的治疗效果。方法 38例Ⅰb2期和Ⅱa期宫颈癌患者中16例行术前子宫动脉灌注介入化疗,用顺铂80mg/m2,化疗2～3疗程。每次介入治疗间隔10～14d。化疗后3～4周行广泛子宫切除术＋盆腔淋巴结清扫术。22例直接行广泛子宫切除术＋盆腔淋巴结清扫术两种治疗方法。结果 16例患者经介入化疗后CR4例,PR10例,总有效率为87.5%。所有患者化疗后均行手术切除。与直接手术患者比较,手术时间和出血量明显减少（P〈0.05,P〈0.005）,术后病理发现肿瘤深肌浸润明显减少（P〈0.05）。结论介入治疗对局部晚期以上宫颈癌有一定的近期疗效,可以提高手术切除率,是宫颈癌综合治疗的有效手段之一。     

局部晚期宫颈癌新辅助动脉化疗40例疗效分析

目的 探讨局部晚期宫颈癌新辅助动脉化疗(neoadjuvant intra-arterial chemotherapy,NAIC)的疗效.方法 分析我科2006年1月～2008年6月期间收治采用TBP方案(紫杉醇脂质体、博来霉素、顺铂)新辅助动脉化疗的局部晚期宫颈癌40例,化疗1～2周期后行广泛子宫切除+盆腔淋巴结清扫...     

Pharmacotherapy of bladder cancer – practice and prospects

In contrast to the US, the incidence and mortality rates of bladder cancer are still increasing in some European countries, despite the fact that most new cases are diagnosed as early, superficial tumours. The standard of care of superficial tumours consists of cytoscopic electroresection of the tumour followed by intravesical immunotherapy or chemotherapy. Immunotherapy with bacillus-Calmette Guerin (BCG) prevents recurrence in most treated patients and has a positive impact on survival; however, ~ 30% are BCG-refractory, progressive tumours. Pharmacogenomics will enable to distinguish those high-risk patients in clinical practice soon. New immunotherapy approaches, such as BCG combined with low-dose interferon or recombinant BCG strains, are promising approaches which need to be explored in prospective trials. The use of neoadjuvant or adjuvant chemotherapy is still controversial but the results of recent trials of neoadjuvant chemotherapy in locally-advanced bladder tumours convinced some leading centres to implement neoadjuvant chemotherapy in selected groups of patients. By far, the four-drug methotrexate–vinblastine–doxorubicin–cisplatin regimen was widely used in metastatic and locally-advanced disease. Recently, two-drug combination gemcitabine–cisplatin proved to be equally effective and less toxic. New chemotherapies tested in clinical trials include gemcitabine, taxanes and new drugs that interfere with signal transduction. Individualisation of established and investigational treatment options based on molecular tumour characteristics, such as p53 status, is probably the future of bladder cancer pharmacotherapy.