According to an article recently published in the New England Journal of Medicine, expression of two proteins, RRM1 and ERCC1, can help predict which patients with early-stage non–small cell lung cancer have an excellent prognosis following surgery alone.

Lung cancer is the leading cause of cancer-related deaths worldwide. Non–small cell lung cancer (NSCLC) is named for the type of cell within the lung where the cancer originated. It and accounts for approximately 75–80% of all lung cancers.

Early NSCLC refers to cancer that has not spread from the lung to distant sites in the body. One component of treatment for early-stage NSCLC is the surgical removal of the cancer, if possible. Some patients may also receive chemotherapy following surgery, referred to as adjuvant chemotherapy. Adjuvant chemotherapy has demonstrated an improvement in survival compared with no chemotherapy for patients with early-stage NSCLC. However, this improvement in survival remains small and may pose a threat to some patients as they may not be able to tolerate the side effects associated with chemotherapy. Researchers continue to evaluate variables that may help predict which patients may benefit from the addition of adjuvant chemotherapy. These findings may help to individualize treatment options and spare patients who do not benefit from the addition of chemotherapy from its side effects.

Researchers from the Lee Moffitt Cancer Center in Florida recently conducted a clinical study to evaluate the potential association between specific proteins and treatment outcomes of patients with early NSCLC. This study included 187 patients with early (Stage I) NSCLC who underwent treatment with surgery only. Levels of the proteins RRM1 (regulatory subunit of ribonucleotide reductase), ERCC1 (excision repair cross-complementation group 1), and PTEN (phosphatase and tensin homologue) were all evaluated from these patients’ cancers specimens. Their outcomes were compared. All of these proteins are involved in the synthesis or repair of DNA.

Approximately 30% of patients had high levels of RRM1 and ERCC1 protein expression; these patients experienced the greatest overall and cancer-free survivals. PTEN levels were not associated with outcomes of patients. Patients were divided into four groups determined by the expression of RRM1 and ERCC1: high levels of RRM1 and high levels of ERCC1 expression (high/high), high levels of RRM1 and low levels of ERCC1 expression (high/low), low levels of RRM1 and high levels of ERCC1 expression (low/high), and low levels of both RMM1 and ERCC1 expression (low/low).

  • Median cancer-free and overall survival exceeded 10 years for patients in the high/high group.
  • Median cancer-free survival was 56 months and overall survival was 80 months for patients in the high/low group.
  • Median cancer-free survival was 51 months and overall survival 57 months for those in the low/high group.
  • Median cancer free survival was 61.4 months and overall survival 66.5 months for those in the low/low group.

The researchers concluded that patients with early-stage NSCLC with high levels of RRM1 and ERCC1 expression have an excellent prognosis following surgery alone and may be able to forego adjuvant chemotherapy. The authors state that “a trial comparing the currentstandard of care with adjuvant treatment selected on the basisof RRM1 and ERCC1 expression appears to be warranted.”

Patients diagnosed with early-stage NSCLC may wish to speak with their physician regarding their individual risks and benefits of participating in a clinical trial further evaluating these protein markers or other markers and associated outcomes to help individualize therapeutic approaches for patients. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and www.eCancerTrials.com.

Reference: Zheng Z, Chen T, Li X, et al. DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. New EnglandJournal of Medicine. 2007; 356:800-808.

Related News:ERCC1 Predicts Responses to Chemotherapy in Early Lung Cancer (9/7/2006)

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