Recent progress in the pharmacotherapy of cancer pain

Cancer pain can be relatively well managed with primary therapies, according to the WHO ladder. However, different conditions may limit the response to the analgesic drug used, which are mainly oploids. Specifically, adverse effects may prevail against the analgesic activity in the clinical setting. New pharmacological strategies may enable a more satisfactory response to be obtained, in terms of balance between analgesia and adverse effects. The change of route of administration or the use of alternative opioids is a first-line option. The use of adjuvant drugs may also improve analgesia with different mechanisms. Recent studies have demonstrated the value of these alternative approaches. However, most of them require definite confirmation in specific well-designed studies.     

Recent progress in the pharmacotherapy of cancer pain

Cancer pain can be relatively well managed with primary therapies, according to the WHO ladder. However, different conditions may limit the response to the analgesic drugs used, which are mainly opioids. Specifically, adverse effects may prevail against the analgesic activity in the clinical setting. New pharmacological strategies may enable a more satisfactory response to be obtained, in terms of balance between analgesia and adverse effects. The change of route of administration or the use of alternative opioids is a first-line option. The use of adjuvant drugs may also improve analgesia with different mechanisms. Recent studies have demonstrated the value of these alternative approaches. However, most of them require definite confirmation in specific well-designed studies.     

Controversies in the management of intracranial germinomas

Intracranial germinomas are uncommon tumors. In the past, patients have traditionally been diagnosed with a trial of focal radiotherapy without biopsy. If the tumor was radiosensitive, it was presumed to be a germinoma. Because of the minimal morbidity and mortality associated with microsurgical techniques, almost all patients now have a histologic diagnosis and can be treated appropriately. Radiation therapy has been employed for the past three decades in the curative management of this disease. The long-term results have been excellent; however, current approaches have explored the possibility of reducing or even eliminating radiation therapy. This article provides a brief overview of intracranial germinomas and explores the controversies in the surgical, radiotherapeutic, and chemotherapeutic management of this tumor.     

Controversies in the management of oropharynx cancer

Squamous cell carcinomas of the oropharynx account for approximately 25% of all head and neck squamous cell malignancies. Most patients present with locally advanced tumors and require a multimodality approach to treatment, with input from qualified surgeons and radiation and medical oncologists. For organ preservation, concurrent chemoradiotherapy is usually preferred over surgery with adjuvant radiotherapy. Controversies regarding management of particular populations of locally advanced oropharyngeal tumors exist, including whether to include induction chemotherapy before chemoradiation, the use of biologic agents as radiation sensitizers, and how best to manage the neck after definitive treatment. Additionally, infection with human papilloma virus (HPV), particularly HPV-16, is now an established risk factor for head and neck cancer. Most cases involve the oropharynx, and prognosis seems to be much better than for patients with non-HPV- and tobacco-related tumors. Given the distinct differences between these HPV and non-HPV-related cancers, controversy also exists regarding the management of these patient populations, with the concern that HPV-related malignancies may be overtreated. Unfortunately, these and other questions concerning the management of locally advanced oropharyngeal cancers are outstanding. Hence, it is critical that eligible patients are screened for and encouraged to participate in clinical trials.     

Controversies in the management of testicular seminoma

Tremendous progress has been made in the treatment of testicular seminoma over the past 25 years. The advent of curative cytotoxic chemotherapy, even for patients with advanced metastatic disease, has led to a paradigm shift toward minimizing additional oncologic therapies and their potential side effects. Despite these advances, controversial issues still exist in managing patients with this disease. Patients with stage I disease can now be managed successfully with close surveillance or postoperative radiotherapy (RT). Although deemed safe, considerable debate persists about surveillance including issues of compliance, cost, and secondary effects of routine RT. Aside from RT, patients with stage I disease also can be managed with one- or 2-dose single-agent carboplatin. Although this appears safe and efficacious, an ongoing randomized study is underway to compare its effectiveness with that of RT. Residual mass after chemotherapy for seminoma is not uncommon and therapeutic options include observation, RT, or retroperitoneal lymphadenectomy. Although most agree that patients with small (<3 cm) or ill-defined masses can be observed, debate persists as to the optimal management of patients with well-defined masses greater than 3 cm. For many years, patients with bulky retroperitoneal disease (>5 cm) were treated with up-front radiotherapy and chemotherapy at relapse. The high failure rate outside the treatment field has now changed this paradigm to one of up-front chemotherapy.     

某三甲医院“癌痛规范治疗”项目实施前后麻醉性镇痛药使用情况分析

目的:调查我院癌痛规范化治疗（good pain management,GPM）示范病房项目对我院癌痛患者麻醉性镇痛药物规范化使用的促进情况。方法:收集我院GPM项目开展前（2012年）、GPM项目开展后（2016年）,GPM科室（肿瘤科）和非GPM科室（其他科室）门诊及住院癌痛患者麻醉性镇痛药处方数据。结果:GPM科室门诊口服阿片类控缓释剂型比例由2012年的18%上升到2016年91%,明显高于非GPM科室的76%;门诊长疗程处方比例由2012年58%上升到2016年79%,也显著高于非GPM科室的49%。GPM科室病房口服控缓释阿片类药品比例由68.96%提高到90.35%,亦高于非GPM科室的62.62%。GPM科室没有使用杜冷丁控制癌痛。结论:GPM项目实施4年后,GPM科室在癌痛规范化治疗方面有明显进步。与非GPM科室相比,GPM科室癌痛治疗更为积极主动、规范合理。GPM项目促进癌痛规范化用药成效显著。     

Controversies in the management of gastrointestinal stromal tumors

Major advances in the medical treatment of gastrointestinal tumors (GISTs) have improved survival for both patients with advanced disease and those diagnosed with high‐risk primary tumors. The Consensus approaches to best practice management of gastrointestinal stromal tumors, published in this journal in 2008, provided guidance for the management of GIST to both clinicians and regulatory authorities. Since then, clinical trials have demonstrated the benefit of adjuvant imatinib in high‐risk patients, and mature data from advanced GIST studies suggest that a small but significant proportion of patients with advanced disease can achieve long‐term benefit with ongoing imatinib treatment. Other evolving management strategies include the controversial use of palliative or debulking surgery to improve outcomes in advanced GIST and the development of promising new multikinase inhibitors, such as regorafenib, which has established benefit in the third‐line setting. This review provides an update of recent developments in GIST management and discusses new controversies that these advances have generated.     

Controversies in the management of gastrointestinal non-Hodgkin's lymphomas

Although more than a thousand GI non-Hodgkin's lymphomas have been reported, the literature does not indicate a clear optimal therapeutic approach. This is primarily due to histological confusion and to the absence of uniform staging procedures and therapeutic modalities. This overview attempts to summarize controversies in the multidisciplinary approach to GI non-Hodgkin's lymphomas and to introduce a European multicentric prospective randomized study for the treatment of this rare disease.     

Controversies in the surgical management of rectal cancer

At the present time, standard therapy for potentially curable rectal cancer consists of transabdominal surgical resection and adjuvant chemoradiation for American Joint Committee on Cancer stage II/III disease. Controversial issues include the use of local excision as opposed to formal resection and total mesorectal excision (TME) alone without adjuvant therapy. Although early stage tumors are the ideal potential candidates for local excision, clinical staging with endoscopic ultrasound is extremely variable in accurately predicting T and N stage. In addition, even low-grade or T1 tumors are associated with a 7% to 14% chance of nodal metastatic disease. Overall, the risk for local recurrence is higher after local excision but may be reduced by adjuvant therapy. Salvage rates for recurrent disease range from 21% to 91%. In regard to TME, local recurrence rates are an impressive 0% to 12% without adjuvant radiation. However, the addition of radiation therapy may further reduce these already low rates, especially in higher-risk groups. The results of 2 large European studies show acceptable complication rates and the applicability of this technique to a diverse patient population.     

Controversies in the management of stage I seminoma

Current controversies in the treatment of stage I seminoma center on the relative roles of surveillance, adjuvant radiotherapy (RT), and adjuvant single-agent chemotherapy. Surveillance has been studied in over 800 patients, 17.1% of whom have relapsed. There is no evidence that surveillance compromises survival in properly selected, compliant patients. The economic benefit of treating only those patients who relapse is offset by the cost of screening diagnostic studies and salvage therapy, and by issues of patient anxiety and compliance. Other methods of reducing the toxicity of RT include reductions in RT dose and volume. A randomized trial has shown that omission of the pelvic field produces relapse-free survival equivalent to that achieved with pelvic plus para-aortic RT. A similar study is currently evaluating a reduction in RT dose from 30 to 20 Gy. Early results from nonrandomized studies of one or two cycles of single-agent chemotherapy demonstrate efficacy comparable to RT in the adjuvant treatment of stage I seminoma. A randomized trial is underway to determine the equivalence of adjuvant carboplatin (Paraplatin) and RT. Long-term follow-up from these studies will provide information not only on the relative efficacy of these alternative strategies but also on the late effects of therapy, including infertility and second malignancy.     

Controversies in the management of regional nodes in melanoma

The surgical management of the regional lymph node basin of melanoma has undergone significant changes in the past 2 decades, most of which have been guided by prospective randomized trials. Historically, routine elective lymph node dissection was recommended for the management of melanoma regardless of clinical nodal involvement. Subsequent randomized trials failed to show a clear benefit for all patients, and sentinel lymph node (SLN) biopsy emerged as an alternative. Although the prognostic value of SLN biopsy in intermediate-thickness melanoma is well accepted, its value for patients with thin and thick lesions is debated. The therapeutic advantage of removing an involved SLN, and the need for a completion lymph node dissection after the identification of a positive SLN, are areas of continued controversy. This article discusses these issues in the management of the regional lymph node basin in patients with melanoma.     

Controversies in the management of early-stage germ cell tumors

The optimal management of clinical stage I testicular germ cell tumors remains controversial despite a cure rate of 99%. Alternatives for stage I nonseminomas include close surveillance, retroperitoneal lymph node dissection, and chemotherapy. For pure seminomas, the options are surveillance, chemotherapy, and radiation. Understanding the pros and cons of each approach may help in choosing a management plan.     

Controversies in the front-line management of chronic lymphocytic leukemia

Once considered a simple homogeneous disease, chronic lymphocytic leukemia (CLL) is now recognized to be a heterogeneous lymphoid malignancy with patients classified into low, intermediate, and high-risk categories based on traditional and novel prognostic factors. Purine nucleoside analogues have been the standard first-line approach for over a decade. The recognition of synergistic activity between purine analogues, alkylating agents, and monoclonal antibodies has allowed the introduction of many new active combination therapies for treatment of this disease. The paucity of randomized studies determining the efficacy and tolerability of these new regimens, however, has made therapy selection for individual patients complex and cumbersome. At the present time, it remains unclear whether patients with aggressive disease based on molecular features should receive early or alternative treatment strategies. In this review, we summarize the data on combination chemotherapy and chemoimmunotherapy in CLL and propose several key factors that should be taken into consideration when deciding on an initial treatment strategy. The review is intended to discuss and simplify first-line therapy selection for patients with CLL in the era of new prognostic indicators and the better understanding of disease biology.