Northwell Health Cancer Institute & Donald and Barbara Zucker School of Medicine at Hofstra, Lake Success, USA
Received Date: July 26th, 2021; Accepted Date: August 9th, 2021
Although FOLFIRINOX is arguably the most successful combination regimen to be used as an adjuvant, neoadjuvant and first-line treatment for patients with pancreatic cancer patients, this regimen does cause moderate toxicity [1-6]. Therefore, FOLFIRINOX is only recommended for patients with good performance status (Eastern Cooperative Oncology Group Performance Status score of 0-1). Following first-line therapy, few regimens have emerged as second-line treatment in this cancer, such as liposome irinotecan or oxaliplatin with 5-FU [7-9]. Limited data exists on sequential treatment in pancreatic cancer as limited agents are active plus overall survival remains to be brief in majority of these patients . It has also been evidenced in other gastrointestinal malignancies such as colorectal cancers (CRC) that combination chemotherapy can kill more tumor cells if the drug dose is not compromised, while sequential single agent chemotherapy may allow for greater dose intensity and treatment time, potentially meaning greater benefit from each single agent, e.g. MRC FOCUS study, CAIRO study, etc. [11, 12]. In addition, sequentially using single agents might cause less toxicity and impairment of quality of life, but it is not known whether this might compromise survival time. Similar efforts have been performed in other solid tumors, such as breast cancer. Sequential single agent chemotherapy was found to have a positive effect on progression-free survival (PFS) in breast cancer patients, whereas combination chemotherapy was associated with a higher response rate (RR) but also related to higher risk of febrile neutropenia . No difference in overall survival (OS) between these treatment strategies was found .
To evaluate the same, we retrospective compared FOLFIRINOX versus sequential 5-FU, oxaliplatin (FOLFOX) and irinotecan-based regimens (irinotecan or liposomal irinotecan) in patients with advanced pancreatic cancer (APC). Our aim was to investigate whether combination treatment upfront with all active agents is better than sequential administration of these drugs in patients with APC following curative therapy. We analyzed overall survival (OS), progression-free survival (PFS), response rate (RR), and adverse events (AEs) in these patients. Patients received FOLFIRNOX upfront versus sequential therapy in the following order based on patient’s presence of toxicities or preference (FOLFOX —> FOLFIRI, FOLFOX—> liposomal irinotecan/5FU, liposomal irinotecan/5FU —> FOLFOX). Each treatment was administered per NCCN guidelines with regulated staging scans, blood work, and office visits. A total of 55 patients were identified with ECOG PS ≤ 2 and male:female ratio 35:20. Results for FOLFIRINOX, FOLFOX followed by FOLFIRI, FOLFOX followed by liposomal irinotecan/5FU, and vice versa are as follows respectively: PFS 4.0, 3.5, 3.5, and 3.0 months; OS 8.0, 7.5, 7.0, and 8.3 months; RR 10%, (8%, 3%), (9%, 4%), and (3%, 5%). One of the patients in the FOLFIRINOX was able to undergo metastatectomy. Table 1 summarizes the toxicities and dose modifications seen.
This retrospective study showed that upfront FOLFIRINOX versus sequential regimens of oxaliplatin and irinotecan-containing regimens resulted in similar PFS and OS but higher AEs as expected. However, surgery was only possible in patients receiving FOLFIRINOX, though a single patient.
Our findings support the use of sequential treatment in APC who are not potential surgical candidates akin to other tumor types, such as CRC or breast cancer. Combination treatment does not significantly improve OS compared with the sequential use of cytotoxic drugs in cancer. Thus, sequential treatment remains a valid option for patients with APC. Further investigative work is warranted to optimize sequencing of active agents in this setting where prognosis has historically been poor.