Chemoradiotherapy for lung cancer

Chemoradiotherapy is a standard treatment for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. Cisplatin-based chemotherapy with concurrent thoracic radiotherapy yields a 5-year survival rate of ～ 15% for patients with unresectable locally advanced non-small cell lung cancer. The state-of-the-art treatment for limited-stage small cell lung cancer is four cycles of chemotherapy with cisplatin plus etoposide combined with early concurrent twice-daily thoracic irradiation and prophylactic cranial irradiation after complete remission. A 5-year survival rate of ～ 25% is expected among patients treated for limited-stage small cell lung cancer. The incorporation of new agents, including target-based drugs, is one of the most promising strategies for improving the survival of patients.     

Chemoradiotherapy: the new standard care for invasive cervical cancer

Cervical cancer remains a major health problem worldwide, despite advances in screening. For patients with locally advanced stage disease, failure to obtain local-regional control usually results in death. In an effort to improve local-regional tumour control, neoadjuvant and concurrent chemoradiation have been tested. Recently, 5 randomised trials performed by the Gynecologic Oncology Group, Radiation Therapy Oncology Group and the Southwest Oncology Group studying cisplatin-based chemoradiation have demonstrated a significant survival advantage. Three of the trials compared cisplatin-based concurrent chemotherapy and radiation to radiation alone and 2 trials compared cisplatin-based concurrent chemotherapy and radiation to radiation with hydroxyurea. In all trials, cisplatin-based chemotherapy administered concurrently with radiation therapy was the more effective therapy, reducing the risk of death by 30 to 50%. Acute toxicities, principally neutropenia and gastrointestinal, were more common with chemoradiation but were transient and rates of late complications were similar between treatment groups. Based on the results of these 5 randomised trials, the National Cancer Institute released a Clinical Announcement stating that cisplatin-based chemotherapy as used in these trials concurrently with radiation therapy should be the new standard of therapy for high risk early stage and locally advanced stage cervical cancer.     

Amrubicin for non-small-cell lung cancer and small-cell lung cancer

Summary Amrubicin is a totally synthetic anthracycline anticancer drug and a potent topoisomerase II inhibitor. Recently, amrubicin was approved in Japan for the treatment of small- and non-small-cell lung cancers (SCLC and NSCLC). Here, we review the efficacy and toxicities of amrubicin monotherapy and amrubicin in combination with cisplatin for extensive-disease SCLC (ED-SCLC), and of amrubicin monotherapy for advanced NSCLC, as observed in the clinical trials. Recommended dosage for previously untreated advanced NCSLC was 45 mg/m²/day by intravenous administration for 3 days. Dose-limiting toxicities were leucopenia, thrombocytopenia, and gastrointestinal disturbance. Response rate was 27.9% for advanced NSCLC, and 75.8% for ED-SCLC with a median survival time (MST) of 11.7 months. Recommended dosage of amrubicin was 40 mg/m²/day in combination with cisplatin at 60 mg/m²/day, with MST of 13.6 months and 1-year survival rate of 56.1%. In sensitive or refractory relapsed SCLC, response rate was 52 and 50%, progression-free survival was 4.2 and 2.6 months, overall survival was 11.6 and 10.3 months, and 1-year survival rate was 46 and 40%, respectively. These results are promising for the treatment of both NSCLC and SCLC. Further clinical trials will clarify the status of amrubicin in the treatment of lung cancer.     

局部晚期鼻咽癌BPP方案同期放化疗与常规放化疗比较

目的:比较BPP方案同期放化疗加辅助化疗和PF方案诱导化疗加放疗加辅助化疗在局部晚期鼻咽癌治疗的效果与毒副作用。方法:回顾性分析154例接受放化结合治疗的局部晚期鼻咽癌患者。其中74例采用BPP方案同期放化疗加辅助化疗(A组);80例采用PF方案诱导化疗加放疗加辅助化疗(B组)。放疗采用常规技术。结果:全程治疗结束后3mo肿瘤疗效评价:A、B组完全缓解率分别为97·3%、88·8%(P<0·05),3a总生存率分别为79·7%、76·4%(P>0·05),无远处转移生存率分别为72·8%、74·9%(P>0·05),无疾病进展生存率分别为71·7%、66·7%(P>0·05)。A组和B组2～3级恶心、呕吐发生率分别为47·3%、57·5%(P>0·05),白细胞减少的发生率分别为43·3%、27·5%(P<0·05),皮肤反应发生率分别为73·0%、87·5%(P<0·05),口腔黏膜反应发生率分别为66·2%、86·2%(P<0·01)。结论:采用BPP方案同期放化疗治疗局部晚期鼻咽癌近期疗效优于PF方案。3a生存率2组无差异。A组血液毒性较高,B组皮肤黏膜反应较重。     

同步放化疗治疗中晚期宫颈癌的临床疗效观察

目的：探讨同步放化疗治疗中晚期宫颈癌的临床疗效和安全性。方法：120例中晚期宫颈癌患者随机分为观察组和对照组各60例,观察组采用同步放化疗治疗,对照组采用单纯放疗,比较二者的近期临床效果和安全性。结果：观察组近期治疗总有效率为93.33%,高于对照组的78.33%,差异有统计学意义（P〈0.05）;观察组患者2年生存率为80.00%,高于对照组的58.33%,差异具有统计学意义（P〈0.05）;观察组不良反应发生率高于对照组,差异有统计学意义（P〈0.05）,但均能耐受。结论：同步放化疗治疗中晚期宫颈癌具有较高的近期临床疗效和2年生存率,不良反应可逆,值得临床推广。     

Gefitinib for non-small-cell lung cancer treatment

Introduction: Gefitinib is an EGFR tyrosine kinase inhibitor (EGFR-TKI) that demonstrated efficacy in patients with advanced non-small cell lung cancer (NSCLC) across therapy lines. In the first-line setting, recent randomized Phase III trials comparing EGFR-TKIs versus platinum-based doublets demonstrated that in patients harboring an activating EGFR mutation, gefitinib is superior to chemotherapy in terms of response rate, progression-free survival, toxicity profile and quality of life, with a marginal positive effect on survival. In order to choose the best treatment, a molecular characterization is now mandatory, as part of baseline diagnostic procedures.

Areas covered: All published data on gefitinib in lung cancer were analyzed using PubMed. The aim of this review is to summarize activity and safety data from major clinical trials of gefitinib in patients with advanced NSCLC.

Expert opinion: EGFR-TKIs including gefitinib are the best option we can offer today in patients with EGFR mutation, regardless of treatment line. Administration of gefitinib to patients with advanced NSCLC is usually well-tolerated and it also appears to be feasible in special populations characterized by a significantly poorer risk:benefit ratio with standard chemotherapy, like elderly patients and patients with poor performance status.     

Paclitaxel for non-small cell lung cancer

Paclitaxel, a tubulin-binding agent, is widely used for the treatment of non-small cell lung cancer (NSCLC). The combination of paclitaxel and a platinum compound is an approved regimen for the treatment of advanced NSCLC. The dose-limiting toxicity of paclitaxel is myelosuppression when administered on a prolonged infusion schedule, whereas neuropathy is more common with short infusions. Although the 3-weekly schedule of paclitaxel is the commonly utilised regimen for the treatment of advanced NSCLC, the weekly regimens appear to be associated with lesser myelosuppression and neuropathy. A randomised clinical trial is currently underway to compare the efficacy of the weekly versus 3-weekly regimen of paclitaxel, in combination with carboplatin for the treatment of advanced NSCLC. The radiosensitising effect of paclitaxel has led to its incorporation into multi-modality treatment of NSCLC patients in combination with thoracic radiation. Paclitaxel has also demonstrated synergistic interaction with several molecularly-targeted agents and is at present being evaluated in the neoadjuvant and adjuvant treatment settings for early stage NSCLC.     

MicroRNA-targeted therapeutics for lung cancer treatment

Introduction: Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists.

Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease.

Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.     

Anti-growth factor therapy for lung cancer

Lung cancers are the leading cause of cancer death in developed countries. In the USA, lung cancer accounts for 29% of all cancer deaths. The cure rate for lung cancer is low (14%) because the cancer spreads early and because chemotherapy cannot cure metastatic disease. In small cell lung cancer (SCLC) two-thirds of patients present with metastatic disease in a distant organ (stage IV). In non-small cell lung cancers (adenocarcinoma, squamous carcinoma, large cell carcinoma) one-third present with metastatic disease. Initial chemotherapy produces high response rates in both SCLC (85%-90% response rate) and NSCLC (50% response rate) but response duration is short and drug resistance develops rapidly. Growth factors play an important role in the pathogenesis and the progression of lung cancers. Knowledge of the role of these growth factors, their receptors and their signal pathways has produced new therapeutic targets. Compounds developed toward these targets have completed preclinical testing and are now in clinical trials. Some of these compounds are active in both drug sensitive and drug resistant lung cancers. They also produce synergistic growth inhibition when combined with cytotoxic chemotherapeutic agents. Thus, these compounds may provide a new way to overcome drug resistance in lung cancer.     

Paclitaxel for non-small cell lung cancer

Paclitaxel, a tubulin-binding agent, is widely used for the treatment of non-small cell lung cancer (NSCLC). The combination of paclitaxel and a platinum compound is an approved regimen for the treatment of advanced NSCLC. The dose-limiting toxicity of paclitaxel is myelosuppression when administered on a prolonged infusion schedule, whereas neuropathy is more common with short infusions. Although the 3-weekly schedule of paclitaxel is the commonly utilised regimen for the treatment of advanced NSCLC, the weekly regimens appear to be associated with lesser myelosuppression and neuropathy. A randomised clinical trial is currently underway to compare the efficacy of the weekly versus 3-weekly regimen of paclitaxel, in combination with carboplatin for the treatment of advanced NSCLC. The radiosensitising effect of paclitaxel has led to its incorporation into multi-modality treatment of NSCLC patients in combination with thoracic radiation. Paclitaxel has also demonstrated synergistic interaction with several molecularly-targeted agents and is at present being evaluated in the neoadjuvant and adjuvant treatment settings for early stage NSCLC.     

Emerging drugs for non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) accounts for 80% of all lung cancer cases and is the leading cause of cancer mortality. Despite the optimization of chemotherapy regimens, treatment outcomes for advanced disease are still disappointing. The EGFR tyrosine kinase inhibitor, erlotinib, and the recombinant monoclonal antibody against the VEGF, bevacizumab, have proven active in NSCLC. In the BR.21 trial, a 2-month benefit in overall survival was observed for previously treated NSCLC patients who received erlotinib versus placebo. The combination of chemotherapy plus bevacizumab yielded superior overall survival or progression-free survival in one randomized trial in advanced non-squamous NSCLC patients. However, despite the introduction of more effective agents, new treatment strategies are clearly needed in lung cancer management.

The review focuses on a number of new targeted agents/chemotherapy drugs now in clinical trials directed at improving NSCLC management. Mature results regarding their activity and usefulness can be expected in the near future.     

Emerging treatment for ALK-positive lung cancer

Introduction: Lung cancer is associated with poor prognosis and limited benefit from chemotherapy. The treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the discovery of targetable genetic alterations, including the ALK fusion oncogene.

Areas covered: Three drugs have been approved for clinical use in ALK-positive patients – crizotinib, ceritinib and alectinib. Unfortunately, treatment resistance inevitably develops. Several mechanisms of acquired resistance are reported. In this review, we will discuss emerging treatment options in ALK-positive advanced NSCLC and strategies to overcome resistance mechanisms, including newer generation of ALK inhibitors, Hsp90 inhibitors and immunotherapy.

Expert opinion: Tremendous advances have been made in the treatment of ALK-positive lung cancers, but management hurdles still exist, including universal development of resistance to ALK inhibitors and limited CNS activity. Given that specific treatment strategies target distinct patterns of resistance, re-biopsy at the time of progression appears necessary to optimize management. However, there remain many issues in routine clinical application including the burden placed on the patients by serial biopsies and the risks of repeat invasive procedures. Future studies are needed to validate the usage of non- or minimally invasive tests and to determine the optimal orders of utilizing different ALK inhibitors.     

Alectinib for ALK-positive non-small-cell lung cancer

Introduction: Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5% of advanced non-small-cell lung cancer (NSCLC) patients. Despite the initial response, after a median of 1-2 years, ALK-positive patients developed an acquired resistance to the ALK-inhibitor crizotinib. Among the most promising second-generation ALK-inhibitors, alectinib is being investigated in crizotinib-naïve and -resistant ALK-positive NSCLC patients.

Areas covered: The current state-of-the-art of ALK-inhibitors treatment, and in particular the role of alectinib in this setting, is reviewed and discussed. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken.

Expert commentary: Alectinib reports promising results with a good safety profile, becoming a potentially very important option for ALK-translocated NSCLC patients. The preliminary results from the J-ALEX phase III randomized trial performed in ALK-rearranged NSCLC Japanese patients showed a better activity and tolerability of alectinib versus crizotinib.     

肺癌肺叶切除术治疗肺癌的围术期处理

目的探讨肺叶切除术治疗肺癌的围术期处理及并发症的预防。方法将40例肺癌患者均行单侧肺叶切除术,对其术中的处理、术后并发症与病理类型及分期进行分析总结。结果经术前或术中对手术并发症的预防与治疗后,单侧肺叶切除术后并发症:肺部感染9例占22.5%、肺不张/漏气2例占5.0%、吸衰竭1例占2.5%、血管栓塞1例2.5%、其他3例占7.5%。合计术后并发症共16例占40.0%。结论肺癌患者进行肺叶切除术围术期术前或术中对手术并发症的预防与治疗后,能够使肺癌患者顺利度过围术期,达到治疗目的,恢复健康。     

Vinorelbine for non-small cell lung cancer

Importance of the field: Vinorelbine is a ‘third-generation’ vinca alkaloid approved for the treatment of NSCLC. The introduction of ‘third-generation’ drugs (vinorelbine, gemcitabine, taxanes) in platinum combination improved survival of patients with advanced NSCLC, with substantially similar results among the different drugs. Treatment toxicities are considerable in this setting.

Areas covered in this review: This narrative review reports a synthesis of evidence available from published clinical trials, systematic reviews and meta-analyses on the activity and safety of vinorelbine, used as single agent or in combination chemotherapy in patients with NSCLC, from 1990 to 2009.

What the reader will gain: When vinorelbine was administered in a weekly schedule without interruptions, the most common toxicity was neutropenia that often precluded administration of the drug, therefore, reducing the dose intensity. A schedule providing administration of vinorelbine on days 1 and 8 every 3 weeks seemed to improve the tolerability of the drug. Tolerability of the drug did not result lower in the elderly subset. None of the other ‘third-generation’ drugs were clearly better tolerated than vinorelbine. Moreover, in the adjuvant setting, vinorelbine is the only third-generation drug that demonstrated, in combination with cisplatin, a consistent improvement in survival on a long-term basis.

Take home message: Vinorelbine is an active and generally manageable therapeutic option for the treatment of both early and advanced NSCLC.     

Emerging drugs for small-cell lung cancer

Small-cell lung cancer (SCLC) is a rapidly progressing tumor in which chemotherapy has a limited impact on survival. Unfortunately, little progress has been made in the medical management of SCLC during the last 30 years, which is best exemplified by the fact that standard first-line chemotherapy has remained platinum-based over time. On the other hand, improvements in survival have been obtained only with the introduction of innovative radiation strategies such as accelerated hyperfractionation to the thorax for limited-stage disease and prophylactic cranial irradiation for both limited- and extensive-stage disease. However, recent advances in the understanding of SCLC biology have renewed the interest in the clinical development of active drugs for SCLC. In this review, we address the most promising agents under clinical evaluation, discussing both novel chemotherapeutic agents and targeted agents. Particularly, amrubicin, a fully synthetic anthracycline, is a very active agent for SCLC, and ongoing Phase III trials are evaluating this agent either in the first-line setting of extensive-stage or relapsed disease. Among targeted agents, anti-angiogenic strategies and Bcl-2 inhibitors represent the most promising approaches, and they are being specifically tested in combination with and/or as maintenance therapy after first-line platinum-based chemotherapy.     

Emerging drugs for non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) accounts for 80% of all lung cancer cases and is the leading cause of cancer mortality. Despite the optimization of chemotherapy regimens, treatment outcomes for advanced disease are still disappointing. The EGFR tyrosine kinase inhibitor, erlotinib, and the recombinant monoclonal antibody against the VEGF, bevacizumab, have proven active in NSCLC. In the BR.21 trial, a 2-month benefit in overall survival was observed for previously treated NSCLC patients who received erlotinib versus placebo. The combination of chemotherapy plus bevacizumab yielded superior overall survival or progression-free survival in one randomized trial in advanced non-squamous NSCLC patients. However, despite the introduction of more effective agents, new treatment strategies are clearly needed in lung cancer management. The review focuses on a number of new targeted agents/chemotherapy drugs now in clinical trials directed at improving NSCLC management. Mature results regarding their activity and usefulness can be expected in the near future.     

Ganetespib for small cell lung cancer

Introduction: Heat shock proteins (Hsps) are part of a complex network of chaperone proteins that are critically involved in the conformational maturation of intracellular proteins and regulate their degradation via the proteasome system Hsps (especially Hsp70 and Hsp90) are upregulated in many cancers and are potentially attractive therapeutic targets. Ganetespib is a potent non-geldanamycin analogue, and avoids the toxicities associated with older analogues due to its small molecular weight, lipophilicity and the absence of the benzoquinone moiety; strong pre-clinical data support its evaluation in lung cancer, especially small cell lung cancer (SCLC).

Areas covered: The chemical structure of ganetespib, the biology of Hsp90 in cancer and the pharmacokinetic and pharmacodynamic data related to ganetespib are summarized; data from preclinical studies and multiple Phase I-III clinical trials, with a focus on its evaluation in SCLC are reviewed.

Expert opinion: Recent progress made in the treatment of refractory SCLC with immune checkpoint inhibitors and DLL3-directed antibody-drug conjugate have made the development of ganetespib particularly challenging in SCLC. Hsp90 remains a critical therapeutic target. Hsp90 inhibitors with a wider therapeutic index and combinations with drugs targeting iHsp90 co-chaperones such as Cdc37 or Protein Kinase 2 may need to be explored in the future.     

Gefitinib for non-small-cell lung cancer treatment

INTRODUCTION: Gefitinib is an EGFR tyrosine kinase inhibitor (EGFR-TKI) that demonstrated efficacy in patients with advanced non-small cell lung cancer (NSCLC) across therapy lines. In the first-line setting, recent randomized Phase III trials comparing EGFR-TKIs versus platinum-based doublets demonstrated that in patients harboring an activating EGFR mutation, gefitinib is superior to chemotherapy in terms of response rate, progression-free survival, toxicity profile and quality of life, with a marginal positive effect on survival. In order to choose the best treatment, a molecular characterization is now mandatory, as part of baseline diagnostic procedures. AREAS COVERED: All published data on gefitinib in lung cancer were analyzed using PubMed. The aim of this review is to summarize activity and safety data from major clinical trials of gefitinib in patients with advanced NSCLC. EXPERT OPINION: EGFR-TKIs including gefitinib are the best option we can offer today in patients with EGFR mutation, regardless of treatment line. Administration of gefitinib to patients with advanced NSCLC is usually well-tolerated and it also appears to be feasible in special populations characterized by a significantly poorer risk:benefit ratio with standard chemotherapy, like elderly patients and patients with poor performance status.