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GUIDELINES |
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| Year : 2008 | Volume
: 3
| Issue : 6 | Page : 97-99 |
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| Systemic therapy in non-small-cell lung cancer |
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Abdul-Rahman Jazieh1, Ahmed Saadeen2
1 King Abdulaziz Medical City for National Guard, Riyadh, Saudi Arabia
2 Riyadh Military Hospital, Riyadh, Saudi Arabia
Correspondence Address:
Abdul-Rahman Jazieh
Department of Oncology (Mail code 1777) P.O. Box 22490, Riyadh 11426
Saudi Arabia
 Source of Support: None, Conflict of Interest: None  | Check |
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 Abstract | | |
The systemic treatment of lung cancer has evolved rapidly over the last two decades. Systemic therapy has become the standard of care for advanced lung cancer up to the third line.
The addition of antiangiogenesis agents to chemotherapy has proved to be beneficial in the first-line setting. Finally, systemic therapy has proven effective in the adjuvant setting in early-stage lung cancer.
Keywords: Lung cancer, systemic therapy, treatment
How to cite this article:
Jazieh AR, Saadeen A. Systemic therapy in non-small-cell lung cancer. Ann Thorac Med 2008;3, Suppl S2:97-9 |
| Introduction | |  |
The systemic therapy of non-small-cell lung cancer (NSCLC) has evolved significantly over the last 15 years, with significant milestone events. The advancement in this area may have occurred in small increments, but at least it is in the right direction. In addition, a great deal of interest and enthusiasm has been infused into the study of a historically fatal disease which, as the number one cancer killer, has not received the attention it deserved.
While in the early 1990s, administering first line chemotherapy for NSCLC was controversial, the use of systemic therapy in the second and third line is a standard practice at present time.
Multiple studies were unable to show any benefit to the patient with the addition of biological agents to chemotherapy, but antiangiogenic agents broke the rule and showed survival benefits when given along with chemotherapy.
The benefit of systemic therapy was also demonstrated in the management of earlier stages of lung cancer as adjuvant treatment.
In this manuscript, the major evidences in the systemic therapy of NSCLC will be summarized.
| Adjuvant Treatment | | |
Stage IA: No benefit to adjuvant chemotherapy was demonstrated in a convincing manner.
Stage IB: CALBG 9633 was positive for a survival advantage with carboplatin and paclitaxel at 3 years, but this turned out to be not significant after 4 years; this may have been due to the early closure of the study, the small sample size, and the use of carboplatin instead of cisplatin. [1] However, subgroup analysis showed some benefits to patients with lesions larger than 4 cm in diameter. Adjuvant uracil-tegafar (UFT) treatment showed a survival benefit in stage 1B in a randomized study of 979 patients conducted by the Japan Lung Cancer Research Group. Five-year survival was 85% vs. 74% in favor of UFT. [2]
Stage II/III: There are multiple phase III trials that have shown the benefits of chemotherapy to patients with resected stage II and stage III disease, using cisplatin combinations, especially cisplatin with venorelbine. [3],[4],[5] [Table 1]
| Combined Modality Treatment | | |
For locally advanced lung cancer, including stage IIIA and stage IIIB (without pleural effusion), concurrent chemoradiotherapy is the standard of care approach, with surgical resection used in selected cases after the combined treatment. The preferred regimen is a cisplatin-based combination (with etoposide or vinblastin) although carboplatin / paclitaxel is also widely used. [6],[7],[8],[9],[10]
| First-line Therapy for Metastatic Disease | | |
Various randomized clinical trials showed that combination chemotherapy with two agents is better than using a single agent; however, combination chemotherapy with three agents does not add any benefit over that provided by two agents. Therefore, chemotherapy doublet became the standard of care, with a platinum-based regimen being the preferred approach. Platinum combinations with docetaxel, gemcitabine, or paclitaxel, are equivalent. [11] In ECOG 1994, 1207 patients with NSCLC were randomized to receive a reference regimen of cisplatin and paclitaxel or one of three experimental regimens: cisplatin and gemcitabine, cisplatin and docetaxel, or carboplatin and paclitaxel.
The response rate and overall survival did not differ significantly between the four arms. The new chemotherapy agents appear equivalent to each other, except for the venorelbine and cisplatin combination, which was shown to be inferior to docetaxel / platinum combinations in a phase III randomized clinical trial. [12]
Multiple randomized studies were conducted to evaluate the benefits of adding biologic agents to the chemotherapy doublets, including erlotinib, gefitinib, and many other agents. None of these studies revealed any additional benefit with these agents.
The only exception to this pattern was the ECOG 4599 by Sandler et al . In this phase III trial, 842 patients with nonsquamous cell lung cancer were randomized to receive carboplatin and paclitaxel or carboplatin, paclitaxel, and bevacizumab. The response rate, progression-free survival, and median survival was better with the addition of bevacizumab (medial survival was 12.5 vs. 10.2 months; P = 0.0075). Patients with nonsquamous cell cancer may benefit from the combination of bevacizumab, carboplatin, and paclitaxel according to this phase III randomized trial, which showed a 2-month survival advantage for the bevacizumab arm. [13]
| Second-line Therapy | | |
Erlotinib, docetaxel, and pemetrexed are all FDA approved in the second-line setting. Docetaxel was the first agent to be approved in the second-line setting for patients who failed first-line therapy. [14],[15]
Pemetrexed was not inferior to docetaxel in a phase III trial. [16] In this study, 571 patients who failed first-line therapy were randomized to receive premetrexed (500 mg/m 2 every 3 weeks along with vitamin supplements) or docetaxel (75 mg/m 2 ). Both agents showed similar response rates, median survival rates, and 1-year survival. [16]
Erlotinib was also approved as second and third line treatment in NSCLC on the basis of a large randomized placebo-controlled double-blind trial of 731 patients. The response rate was 8.9% for erlotinib and overall survival was 6.7 months vs. 4.7 months for placebo (HR = 0.70; P <0.001). [17]
| Third-line Therapy and Beyond | | |
Only erlotinib is proven to have benefits in the third line setting. [17] No other agent is approved by the regulatory agencies in the third line setting and no evidence of treatment benefit beyond third line of therapy.
In summary, advances have occurred over the last decade in the systemic therapy of NSCLC. The use of the customization and individualized therapy approaches will be the trend of the future.
| References | | |
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| 11. | Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al . Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-8. [PUBMED] [FULLTEXT] |
| 12. | Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, et al . Multinational, phase III Study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: The TAX 326 study group. J Clin Oncol 2003;21:3016-24. [PUBMED] [FULLTEXT] |
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[Table 1] |
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