Calmangafodipir, an investigational cytoprotective agent, reduces oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer (mCRC) without affecting chemotherapy efficacy, the phase II PLIANT study has shown.

In 173 mCRC patients on the FOLFOX-6 (oxaliplatin, leucovorin, 5-FU) regimen, administration of calmangafodipir (5 or 10 µmol/kg) 10 minutes prior to each chemotherapy cycle reduced the frequency, onset and duration of grade ≥2 chemotherapy-induced peripheral neuropathy (CIPN) compared with placebo. [Multinational Association of Supportive Care in Cancer Annual Meeting 2015, abstract 27-01-O]

Overall reduction in grade ≥2 CIPN was 43 percent with the 5 µmol/kg dose of calmangafodipir (p=0.146). When patients treated with bevacizumab were excluded, the reduction in grade ≥2 CIPN reached statistical significance for the 5 and 10 µmol/kg doses combined (p=0.025).

Reductions in cold allodynia and paresthesia were also seen with calmangafodipir.

“Importantly, unlike other strategies that have been used to prevent CIPN, calmangafodipir showed no apparent negative impact on the efficacy of chemotherapy,” said principal investigator Dr. Devalingam Mahalingam of the University of Texas Health Science Centre in San Antonio, TX, US. “The objective response rate was 27 in patients who received calmangafodipir 5 µmol/kg and those who received placebo [p=0.49].”

Calmangafodipir was developed as an improvement on the MRI contrast agent, mangafodipir. “While accumulation of manganese in the brain has been a concern with repeated administration of mangafodipir, calmangafodipir was designed to be safe even with repeated dosing,” said Mahalingam.

“Calmangafodipir had a very benign safety profile in the PLIANT study,” he continued. “Neurotoxicity was very low, as was the incidence of grade 3/4 neutropenia.”

While more data are needed to define the benefit of calmangafodipir in CIPN prevention, researchers from the North Central Cancer Treatment Group recently characterized the clinical course of oxaliplatin-induced neuropathy using data from the phase III study NO8CB. [J Clin Oncol 2015, doi:10.1200/JCO.2014.58.8533]

They found that in patients with colon cancer receiving adjuvant FOLFOX, symptoms of acute oxaliplatin-induced neuropathy were only half as severe in cycle 1 compared with subsequent cycles. The acute symptoms, including sensitivity to touching or swallowing cold items (71 percent), throat discomfort (63 percent) or muscle cramps (42 percent), usually peaked at day 3 of each cycle and improved afterwards. However, they did not always resolve completely between cycles.

Symptoms of chronic neurotoxicity, including tingling, numbness and pain, were more prominent in the hands during chemotherapy. By 18 months, however, the symptoms became more severe in the feet.

“Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity,” the authors wrote.

Calmangafodipir, an investigational cytoprotective agent, reduces oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer (mCRC) without affecting chemotherapy efficacy, the phase II PLIANT study has shown.

In 173 mCRC patients on the FOLFOX-6 (oxaliplatin, leucovorin, 5-FU) regimen, administration of calmangafodipir (5 or 10 µmol/kg) 10 minutes prior to each chemotherapy cycle reduced the frequency, onset and duration of grade ≥2 chemotherapy-induced peripheral neuropathy (CIPN) compared with placebo. [Multinational Association of Supportive Care in Cancer Annual Meeting 2015, abstract 27-01-O]

Overall reduction in grade ≥2 CIPN was 43 percent with the 5 µmol/kg dose of calmangafodipir (p=0.146). When patients treated with bevacizumab were excluded, the reduction in grade ≥2 CIPN reached statistical significance for the 5 and 10 µmol/kg doses combined (p=0.025).

Reductions in cold allodynia and paresthesia were also seen with calmangafodipir.

“Importantly, unlike other strategies that have been used to prevent CIPN, calmangafodipir showed no apparent negative impact on the efficacy of chemotherapy,” said principal investigator Dr. Devalingam Mahalingam of the University of Texas Health Science Centre in San Antonio, TX, US. “The objective response rate was 27 in patients who received calmangafodipir 5 µmol/kg and those who received placebo [p=0.49].”

Calmangafodipir was developed as an improvement on the MRI contrast agent, mangafodipir. “While accumulation of manganese in the brain has been a concern with repeated administration of mangafodipir, calmangafodipir was designed to be safe even with repeated dosing,” said Mahalingam.

“Calmangafodipir had a very benign safety profile in the PLIANT study,” he continued. “Neurotoxicity was very low, as was the incidence of grade 3/4 neutropenia.”

While more data are needed to define the benefit of calmangafodipir in CIPN prevention, researchers from the North Central Cancer Treatment Group recently characterized the clinical course of oxaliplatin-induced neuropathy using data from the phase III study NO8CB. [J Clin Oncol 2015, doi:10.1200/JCO.2014.58.8533]

They found that in patients with colon cancer receiving adjuvant FOLFOX, symptoms of acute oxaliplatin-induced neuropathy were only half as severe in cycle 1 compared with subsequent cycles. The acute symptoms, including sensitivity to touching or swallowing cold items (71 percent), throat discomfort (63 percent) or muscle cramps (42 percent), usually peaked at day 3 of each cycle and improved afterwards. However, they did not always resolve completely between cycles.

Symptoms of chronic neurotoxicity, including tingling, numbness and pain, were more prominent in the hands during chemotherapy. By 18 months, however, the symptoms became more severe in the feet.

“Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity,” the authors wrote.

Calmangafodipir, an investigational cytoprotective agent, reduces oxaliplatin-induced neuropathy in patients with metastatic colorectal cancer (mCRC) without affecting chemotherapy efficacy, the phase II PLIANT study has shown.

In 173 mCRC patients on the FOLFOX-6 (oxaliplatin, leucovorin, 5-FU) regimen, administration of calmangafodipir (5 or 10 µmol/kg) 10 minutes prior to each chemotherapy cycle reduced the frequency, onset and duration of grade ≥2 chemotherapy-induced peripheral neuropathy (CIPN) compared with placebo. [Multinational Association of Supportive Care in Cancer Annual Meeting 2015, abstract 27-01-O]

Overall reduction in grade ≥2 CIPN was 43 percent with the 5 µmol/kg dose of calmangafodipir (p=0.146). When patients treated with bevacizumab were excluded, the reduction in grade ≥2 CIPN reached statistical significance for the 5 and 10 µmol/kg doses combined (p=0.025).

Reductions in cold allodynia and paresthesia were also seen with calmangafodipir.

“Importantly, unlike other strategies that have been used to prevent CIPN, calmangafodipir showed no apparent negative impact on the efficacy of chemotherapy,” said principal investigator Dr. Devalingam Mahalingam of the University of Texas Health Science Centre in San Antonio, TX, US. “The objective response rate was 27 in patients who received calmangafodipir 5 µmol/kg and those who received placebo [p=0.49].”

Calmangafodipir was developed as an improvement on the MRI contrast agent, mangafodipir. “While accumulation of manganese in the brain has been a concern with repeated administration of mangafodipir, calmangafodipir was designed to be safe even with repeated dosing,” said Mahalingam.

“Calmangafodipir had a very benign safety profile in the PLIANT study,” he continued. “Neurotoxicity was very low, as was the incidence of grade 3/4 neutropenia.”

While more data are needed to define the benefit of calmangafodipir in CIPN prevention, researchers from the North Central Cancer Treatment Group recently characterized the clinical course of oxaliplatin-induced neuropathy using data from the phase III study NO8CB. [J Clin Oncol 2015, doi:10.1200/JCO.2014.58.8533]

They found that in patients with colon cancer receiving adjuvant FOLFOX, symptoms of acute oxaliplatin-induced neuropathy were only half as severe in cycle 1 compared with subsequent cycles. The acute symptoms, including sensitivity to touching or swallowing cold items (71 percent), throat discomfort (63 percent) or muscle cramps (42 percent), usually peaked at day 3 of each cycle and improved afterwards. However, they did not always resolve completely between cycles.

Symptoms of chronic neurotoxicity, including tingling, numbness and pain, were more prominent in the hands during chemotherapy. By 18 months, however, the symptoms became more severe in the feet.

“Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity,” the authors wrote.