Pemetrexed (Alimta) is the standard chemotherapy drug for mesothelioma treatment. To increase its efficacy, medical oncologists often combine it with a platinum-based chemotherapy drug like cisplatin or carboplatin.

However, adding a second drug also increases the risk for (and severity of) chemotherapy-induced side effects.

These side effects can prevent patients from completing a full chemotherapy cycle. They can also discourage patients from pursuing  adjuvant therapies, such as surgery or radiation therapy.

Weighing the Options

To design a treatment program with the highest possible chance of success, doctors need to choose a drug (or drug combination) with a ratio that is appropriate for the patient’s unique condition. Their goal is to find a tolerable dose without sacrificing efficacy.

To  explore the risk-benefit ratios of common chemotherapy combinations, a study in December’s Anticancer Research tracked the tolerability and anti-cancer activity of pemetrexed + carboplatin and pemetrexed + cisplatin.

The study looked at 51 mesothelioma patients who received chemotherapy at the University Hospital in Padua, Italy. (Of the group, 27 patients paired pemetrexed with carboplatin; 24 paired it with cisplatin).

The Risks

During and after the chemotherapy treatments, patients in the pemetrexed-cisplatin group had higher side effect rates. These patients more frequently developed grade 3 anemia and cumulative grade 2-3 asthenia (fatigue).

Patients in the pemetrexed-cisplatin group also reported a poorer performance status throughout the study.

Neither group reported any incidence of grade 4 toxicity. However, doctors did reduce the dose for two of the patients in the cisplatin group because of excessively-high side effects.

The Benefits

Eligible patients underwent surgery and radiotherapy, and at the end of the trimodal treatment, both groups displayed similar improvements. Both drug combinations produced similar rates for progression-free survival, response and disease control:

• 4 percent of pemetrexed-carboplatin patients had a complete response, compared to 0 percent of the patients in the pemetrexed-cisplatin group.

• 18 percent of pemetrexed-carboplatin patients had a partial response, compared to 17 percent of the patients in the pemetrexed-cisplatin group.

• 74 percent of pemetrexed-carboplatin patients had stable disease, compared to 79 percent of the patients in the pemetrexed-cisplatin group.

Patients in the carboplatin group were also more likely to complete the full trimodal treatment plan.

Carboplatin Called ‘Gentler’ Regimen

Overall, the researchers felt that the risk profile was slightly higher in the cisplatin group, while the benefit profile was similar for both drug combinations. This led them to label the carboplatin combination the “gentler” approach.

They determined carboplatin may be a better complement to pemetrexed in patients who are scheduled to later receive a mesothelioma surgery. They also determined that the carboplatin regimen may be more appropriate for elderly patients, patients with several other diseases or patients with an impaired performance status.