Marwan G. Fakih, MD: Tolerability as a Factor in Therapy

Is tolerability a factor in determining subsequent therapy?

Dr. Fakih believes this patient is clearly symptomatic, with a high burden of disease. Dr. Fakih says that it is not just about prolonging this patient's survival, but also about palliative impact of chemotherapy on this patient. Tumor reduction is important so that he can breathe better. In addition he has a significant load of disease in the liver that should be gotten rid of. A strategy that decreases the volume of metastatic disease in the liver to avoid the potential of going into liver failure is important.

Dr. Fakih says that one must think of the response rates in patients who have progressed on first-line chemotherapy that is oxaliplatin-based, in the setting of second-line treatments. With FOLFIRI plus antiangiogenic therapies, in patients who have progressed on bevacizumab-based treatment with first-line therapy, the objective response rate is less than 10 percent. Despite the fact that it is likely to be able to control the disease in this patient for an average of approximately six months with second-line treatment in this setting, it is unlikely that the downstage of the disease is significant and quick enough to make him feel better quickly.

CASE 1: Metastatic Colorectal Cancer (CRC)

Neil H. is a 62-year-old construction manager from Houston, Texas.

• His prior medical history is notable for obesity, mild hypertension, hyperuricemia, and gout

The patient was diagnosed with colon cancer in February 2011, after reporting to his PCP with symptoms of intermittent nausea, vomiting, and blood in his stool

• Patient underwent resection of the sigmoid colon with lymph node evaluation (12 nodes examined), which showed adenocarcinoma stage T3N0M0; mutational status showed RAS WT; BRAF negative

In January of 2013, he presented to his oncologist for evaluation after his CEA had increased to 85 ng/mL.

The patient was asymptomatic at the time of recurrence

CT scan showed multiple unresectable metastatic lesions to the liver and lung; the patient’s ECOG performance status was 0

He received initial therapy with FOLFOX and bevacizumab for metastatic disease

After 6 cycles the patient experienced a good response but developed grade 3 neuropathy and oxaliplatin was discontinued

The patient was continued on 5FU with bevacizumab with eventual improvement of his neuropathy symptoms; his disease continued to be stable

In February of 2015, the patient presents with fatigue, nonexertional dyspnea, and cough, and his CEA had increased to 110 ng/mL.

• CT scan was consistent with progression of liver and pulmonary lesions