Lung Cancer

Targeted therapies inhibiting the epidermal growth factor receptor(EGFR) have been introduced in the treatment of patients with advancednon–small-cell lung cancer (NSCLC). Many inhibitors of theEGFR have been developed, targeting either the extracellular receptordomain with antibodies or the intracellular tyrosine kinase bindingdomain with small molecules. The tyrosine kinase inhibitor (TKI)gefitinib (Iressa) was the first targeted drug to be registered for thetreatment of NSCLC after failure of chemotherapy. Given concurrentlytogether with platinum combination chemotherapy both TKIs gefitiniband erlotinib (Tarceva) failed to increase activity. Sequential targetedtherapy after chemotherapy is currently being investigated further. Studieswith the monoclonal antibody cetuximab (Erbitux) combined withchemotherapy are ongoing. Side effects of the small molecules aremainly skin rash and diarrhea, whereas the antibodies do not give diarrhea.Selection of patients, based on molecular markers and patientcharacteristics, has become an important issue for the further developmentof these drugs, given there is activity in a relatively small group ofpatients with NSCLC. Newer drugs inhibiting more than one receptorpathway are being investigated in order to find activity in a broadergroup of patients.

In their excellent review of firstlinechemotherapy for patientswith advanced non–small-cell lungcancer (NSCLC), Laskin and Sandlerare clear, direct, and positive. Chemotherapyworks in stage IV disease:

With best supportive care alone, patients with metastatic non–smallcelllung cancer (NSCLC) have a median survival of 4 to 5 months anda 1-year survival rate of approximately 10%. Trials carried out in the1980s and 1990s comparing chemotherapy to best supportive care reportedvariable efficacy results; however, a pivotal meta-analysis of thesedata indicated that cisplatin-based chemotherapy provided a survivalbenefit in advanced NSCLC. In the past decade newer agents such asgemcitabine (Gemzar), vinorelbine, paclitaxel, and docetaxel (Taxotere)have all demonstrated activity in NSCLC as single agents; consequentlythese agents have been combined with cisplatin or carboplatin. Randomizedphase III trials comparing these “newer” platin-based doubletshave failed to identify an optimal platinum-based doublet therapyregimen. Though it is clear that chemotherapy is an appropriate treatmentfor many patients with lung cancer, there a sense in which the useof traditional chemotherapeutic agents has reached a therapeutic plateau.Increased understanding of cancer biology has revealed numerouspotential therapeutic strategies, including targeting the epidermalgrowth factor receptor, protein kinase C, rexinoid receptors, and theangiogenesis pathway. The Eastern Cooperative Oncology Group studyE4599 comparing paclitaxel/carboplatin with/without bevacizumab isthe first phase III randomized trial to show a survival advantage withthe addition of a molecularly targeted agent to chemotherapy in thechemotherapy-naive patient population. Future studies will involve theevaluation of additional targeted agents plus chemotherapy as well aslooking at combinations of these targeted agents alone or with chemotherapy.

LEIDEN, The Netherlands-In a prospective 100-patient study that may have direct applicability to clinical practice, a team of Dutch researchers has demonstrated improved identification of mediastinal tumor invasion (T4) or lymph node metastases (N2/N3) in patients with non-small-cell lung cancer (NSCLC) when preoperative staging employed transesophageal ultrasound–guided fine-needle aspiration (EUS-FNA) in addition to mediastinoscopy. The finding, they said, is attributable to the "complementary reach" of these diagnostic tools in assessing regional lymph node stations and in the ability of EUS-FNA to detect mediastinal tumor invasion.

The patient is a 74-year-old gentleman who presented with a visual disturbance and right shoulder pain. On routine chest x-ray, he was found to have a right apical lung mass.

Only about 15% of patients diagnosed with lung carcinoma eachyear are surgical candidates, either due to advanced disease orcomorbidities. The past decade has seen the emergence of minimallyinvasive therapies using thermal energy sources: radiofrequency,cryoablation, focused ultrasound, laser, and microwave; radiofrequencyablation (RFA) is the best developed of these. Radiofrequency ablationis safe and technically highly successful in terms of initial ablation.Long-term local control or complete necrosis rates drop considerablywhen tumors are larger than 3 cm, although repeat ablations can beperformed. Patients with lung metastases tend to fare better with RFlung ablation than those with primary lung carcinoma in terms of localcontrol, but it is unclear if this is related to smaller tumor size at time oftreatment, lesion size uniformity, and sphericity with lung metastases,or to differences in patterns of pathologic spread of disease. The effectsof RFA on quality of life, particularly dyspnea and pain, as well aslong-term outcome studies are generally lacking. Even so, the resultsregarding RF lung ablation are comparable to other therapies currentlyavailable, particularly for the conventionally unresectable or high-risklung cancer population. With refinements in technology, patient selection,clinical applications, and methods of follow-up, RFA will continueto flourish as a potentially viable stand-alone or complementarytherapy for both primary and secondary lung malignancies in standardand high-risk populations.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

Mesotheliomas are uncommon in the United States, with an incidenceof about 3,000 new cases per year (or a risk of about 11 per million Americansper year). Incidence and mortality, however, are probably underestimated.Most are associated with asbestos, although some have arisen inports of prior radiation, and a reported association with simian virus (SV)40remains controversial. About 85% of mesotheliomas arise in the pleura,about 9% in the peritoneum, and a small percentage in the pericardiumor tunica vaginalis testis. The histology of about half of mesotheliomas isepithelial (tubular papillary), with the remainder sarcomatous or mixed.Multicystic mesotheliomas and well-differentiated papillary mesotheliomasare associated with long survival in the absence of treatmentand should be excluded from clinical trials intended for the usual rapidlylethal histologic variants of the disease. The median survival isunder a year, although longer median survivals for selected patients,particularly those with epithelial histology, have been reported in somecombined-modality studies. Recent randomized trials have shown significantimprovement in time to progression and survival for the additionof new antifolates to platinum-based chemotherapy.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

BARCELONA, Spain-Final results of a large international phase III trial confirm the benefit of adjuvant chemotherapy after complete resection in patients with early-stage non-small-cell lung cancer (NSCLC). Rafael Rosell, MD, of Catalan Institute of Oncology, Badalona, Spain, presented the results of the trial, known as ANITA (Adjuvant Navelbine International Trialist Association), at a plenary session of the 11th World Conference on Lung Cancer. Earlier this year, Jean-Yves Douillard, MD, PhD, head, Division of Medical Oncology, Rene Gauducheau Cancer Center, Saint-Herblain, France, reported the study findings at the American Society of Clinical Oncology 41st Annual Meeting .

ORLANDO - A 2-minute breath test to detect volatile organic compounds (VOCs) successfully predicted lung cancer in patients with stage I-IV disease, according to a study reported by Michael Phillips, MD, at the American Society of Clinical Oncology 41st Annual Meeting (abstract 9510). "The breath test may potentially become a useful adjunct to lung cancer detection," said Dr. Phillips, clinical professor of medicine, New York Medical College, Valhalla.

We applaud Dr. Cappuzzo andcolleagues for an excellentreview of an emerging fieldin lung cancer treatment. Since 2000,three drugs (docetaxel [Taxotere],pemetrexed [Alimta], and erlotinib[Tarceva]) have been approved by theUS Food and Drug Administration(FDA) for second-line therapy in non–small-cell lung cancer (NSCLC) basedon the results of phase III trials (seeTable 1).[1-4] It is also possible thatsimilar approval will be sought for otherdrugs (eg, topotecan [Hycamtin]),[5]and gefitinib (Iressa) remains an optionfor treatment in the third-line setting.

Platinum-based chemotherapy offers a modest survival advantage overbest supportive care in chemotherapy-naive patients with a good performancestatus and advanced/metastatic non–small-cell lung cancer(NSCLC). Despite the survival benefit associated with first-line chemotherapy,the majority of patients will experience relapse or disease progression.In clinical practice, an increasing number of patients maintaina good performance status after first-line treatment and are eligible forfurther treatments. Docetaxel (Taxotere) at 75 mg/m2 given once every3 weeks has been the standard of care for second-line chemotherapy sincethe year 2000. Pemetrexed (Alimta) is a novel multitargeted antifolateagent with single-agent activity in first- and second-line treatment ofNSCLC. A large phase III study comparing docetaxel to pemetrexed insecond-line therapy demonstrated that pemetrexed is equally active andless toxic than docetaxel. Based on these results, pemetrexed is a reasonablesecond-line chemotherapy option for patients with recurrent, advancedNSCLC. Progress made in the field of molecular biology has led to theidentification of drugs active against specific cellular targets. Gefitinib(Iressa) and erlotinib (Tarceva) are both orally active tyrosine kinase inhibitorsof the epidermal growth factor receptor. Phase II and III trialshave demonstrated that these agents are active particularly in a subgroupof patients with specific biologic characteristics. Both drugs have beenapproved for the treatment of pretreated NSCLC. Other drugs, such ascetuximab (Erbitux) and bevacizumab (Avastin) have shown promisingactivity in NSCLC and are currently being tested in clinical trials.

About 172,570 new cases ofnon–small-cell lung cancer(NSCLC) are expected to bediagnosed in 2005 in the United States,and almost as many will die of thedisease. Patients with effusions or metastaticdisease are candidates for combinationchemotherapy. The regimensof choice are platinum-based combinationchemotherapy schedules. Giventhat most patients will experience diseaseprogression despite their initialtreatment, they may be eligible for second-line chemotherapy, provided theyhave an acceptable performance status.