One chemotherapy does not fit all: Make-up of cells could interfere with treatment success

This study examined whether ribonucleotide reductase regulatory subunit M1 is a useful prognostic marker for chemotherapy treatment response in patients with non-small cell lung cancer.

Platinum-based chemotherapy, using a variety of agents, is a main course of treatment for advanced non-small cell lung cancer. However, there is a great deal of variability in how well patients respond to these therapies, and the number and severity of negative side effects they experience. Recent evidence has shown that the presence of certain markers (such as levels of proteins or molecules in the body) or genetic mutations can predict how a patient may react to a certain therapy, which can be a useful tool in targeting therapies to individuals.

Ribonucleotide reductase regulatory subunit M1 (RRM1) is a protein involved in DNA creation and repair. Low levels of RRM1 in patients with non-small cell lung cancer have been associated with higher response rates to gemcitabine (Gemzar)-based chemotherapy. Other studies, however, have not found this association.

The current study examined the association between RRM1 and the response to platinum-based chemotherapies. This study reviewed the records of 229 advanced non-small cell lung cancer patients who received carboplatin (Paraplatin)-based chemotherapy: 35.4% of patients received gemcitabine, 33.6% received docetaxel (Taxotere) and 31.0% received vinorelbine (Navelbine).

63.8% of the patients were determined to be RRM1 negative, and 36.2% were RRM1 positive. There were no overall differences in treatment response rates for the positive or negative patients. However, 78.8% of RRM1-negative patients receiving gemcitabine showed a response lasting longer than 3 months, compared to 55.2% of the RRM1-positive patients receiving the same type of chemotherapy.

The average progression-free survival time (time before disease recurs or progresses) for all patients was 8.7 months; there were no overall differences between RRM1-positive and -negative patients. Progression-free survival times were significantly longer for RRM1-negative patients receiving gemcitabine (8.8 months) compared to RRM1-positive patients (7.6 months) receiving gemcitabine.

81.5% of RRM1-positive patients who were treated with docetaxel or vinorelbine showed a complete or partial response following treatment, compared to 55.2% for RRM1-positive patients receiving gemcitabine.

This study concluded that a lack of RRM1 is associated with worse response and progression-free survival rates in non-small cell lung cancer patients receiving gemcitabine-based chemotherapy.