The Oncology Brothers—Rahul Gosain, MD, MS, and Rohit Gosain, MD—invited Rachna Shroff, MD, MS, FASCO, of the University of Arizona Cancer Center, and Midhun Malla, MD, of the University of Alabama at Birmingham, to share their knowledge on managing the adverse effects of 2 key pancreatic cancer treatments: FOLFIRINOX (leucovorin calcium [folinic acid], fluorouracil [5-FU], irinotecan hydrochloride, and oxaliplatin) and gemcitabine plus nab-paclitaxel.
Given the nature of this cancer, keeping patients on therapy for as long as possible while preserving quality of life is a key goal of treatment, Dr. Rahul Gosain emphasized.
5-FU and Leucovorin Toxicities
A major consideration of FOLFIRINOX is bolus or continuous administration of the 5-FU component. Bolus 5-FU is linked to toxicities such as myelosuppression, stomatitis, mucositis, and diarrhea. The doctors agreed that in the metastatic setting, dropping bolus administration is a smart approach to managing toxicities.
“Most of us modify FOLFIRINOX,” Dr. Shroff said. “In almost all of my patients, I tend to eliminate the bolus 5-FU and the leucovorin, and it’s really to mitigate the toxicities that can sometimes be overlapping between the FOLFIRINOX regimen.”
Dr. Malla agreed, highlighting an analysis of over 11,000 patients in JNCCN that found omitting first-line bolus 5-FU led to reduced toxicity without compromising efficacy. He noted that he’s a bit hesitant to omit bolus 5-FU in the curative setting. He prefers to attempt 1 or 2 treatments, with a low threshold for switching to continuous 5-FU if bolus toxicities prevent the patient from receiving the next cycle.
Compared to bolus, continuous 5-FU has a slightly different toxicity profile that includes palmar-plantar erythrodysesthesia (hand-foot syndrome). In the rare event of coronary vasospasms, Dr. Shroff recommended collaborating with cardiologists for mitigating agents.
If 5-FU must be halted completely, Dr. Shroff stressed that oxaliplatin won’t be effective, although irinotecan has some single-agent efficacy.
In the doctors’ experiences, the key toxicity of oxaliplatin is neuropathy. Dr. Shroff emphasized the need to manage this adverse effect to prevent more severe events; she typically uses pregabalin, gabapentin, or duloxetine for neuropathy.
Dr. Malla noted that some patients on oxaliplatin develop hyperpigmentation of the skin, particularly around the fingers, and altered taste. To address the latter, he recommends advising patients to brush their teeth before eating or use an oral rinse with baking soda.
Some data also supports the efficacy of cryotherapy, acupuncture, and physical therapy in managing neuropathy and other adverse effects. Overall, the doctors agreed that different strategies work for different patients, and the choice between adjusting the dose or dropping oxaliplatin altogether may vary between the curative and palliative settings.
Irinotecan and nal-IRI Toxicities
With traditional irinotecan, the major toxicities are diarrhea, nausea, vomiting, and myelosuppression. Dr. Malla noted that he prefers to start treatment at a dose of 150 mg/m2 in the metastatic setting. Furthermore, evaluating dihydropyrimidine dehydrogenase and UDP-glucuronosyltransferase levels can help guide potential dose adjustments.
Although nanoliposomal irinotecan (nal-IRI) is described as more tolerable, Dr. Shroff cautioned that it can cause diarrhea that’s hard to control. She advised educating patients on antidiarrheals and having them take imodium and lomotil at the first sign of adverse effects.
Dr. Malla said that he ensures patients know the daily maximum limit of imodium so they don’t underuse it, and he sometimes writes a prescription for imodium in the hopes of increasing patient adherence.
Drs. Malla and Shroff both cautioned against viewing diarrhea events strictly based on grade, noting that grade 2 can have a significant impact on quality of life and lead to dehydration.
Nab-paclitaxel and Gemcitabine Toxicities
Among the toxicities of gemcitabine and nab-paclitaxel, the doctors highlighted myelosuppression, peripheral neuropathy, fatigue, and elevated bilirubin.
Dr. Shroff stated that she typically administers gemcitabine with nab-paclitaxel every 14 days, rather than on the schedule initially described in the MPACT trial. In her experience, this cadence reduces some of the myelosuppressive effects and helps avoid the need for growth factor supporting agents.
On the question of starting older patients on single-agent gemcitabine and then adding nab-paclitaxel, Drs. Shroff and Malla suggested that performance status, not age, should guide treatment intensity.
Ultimately, all 4 doctors agreed that communicating with patients and basing a plan on the treatment setting is crucial for appropriately managing the adverse effects of FOLFIRINOX and gemcitabine with nab-paclitaxel in pancreatic cancer.
