A 58-year-old with Stage IV Pancreatic Adenocarcinoma - Cancer Therapy Advisor

A 58-year-old with Stage IV Pancreatic Adenocarcinoma

Slideshow

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Chief Complaint

R.M. is a 58-year-old male recently diagnosed with stage IV pancreatic adenocarcinoma (Slide 1). He is a mechanical engineer and intends to continue to work from home during his treatment. He is 10 days from a stent placement for hyperbilirubinemia (Slide 2).

Relevant Medical History

• Hypertension

• Diabetes (well-controlled)

• Hypercholesterolemia

• Depression

Laboratory Tests/Clinical Presentation

• Eastern Cooperative Oncology Status (ECOG) performance status of 1.

• Renal function and liver function are within normal limits.

• Blood pressure is 13/80 mm Hg.

• No peripheral neuropathy.

Initial Treatment Plan

R.M.’s oncologist decides on FOFIRINOX treatment based on his ECOG status and age (Slide 3). After three cycles, his ECOG performance status worsens to 2. In addition, he experiences grade 2 vomiting and grade 3 thrombocytopenia. Liver function and renal function remain within normal limits.

The correct answer is Gemcitabine + nab-paclitaxel.Explanation Gemcitabine plus erlotinib, FOLFIRINOX, and gemcitabine plus nab-paclitaxel all are designated Category 1 in the 2013 NCCN guidelines and therefore they are appropriate options for stage IV adenocarcinoma of the pancreas.1 However, none...

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The correct answer is Gemcitabine + nab-paclitaxel.

Explanation

Gemcitabine plus erlotinib, FOLFIRINOX, and gemcitabine plus nab-paclitaxel all are designated Category 1 in the 2013 NCCN guidelines and therefore they are appropriate options for stage IV adenocarcinoma of the pancreas.1 However, none of the aforementioned regimens have been studied head-to-head; the comparator of each of the regimens has been single-agent gemcitabine. Of the regimens with Category 1 designation, FOLFIRINOX has the best median survival with 11 months compared with 6.9 months with single-agent gemcitabine (Slide 4).2 However, it was associated with significant toxicity including neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, and sensory neuropathy. In the clinical trial of FOLFIRINOX, patients were included if they had an ECOG performance score of 0-1. The median age in the study was 61 years of age. The next option to consider would be gemcitabine + nab-paclitaxel. In this study, gemcitabine + nab-paclitaxel had a superior median overall survival compared with single-agent gemcitabine with 8.5 months versus 6.7 months.3 The toxicity profile of gemcitabine + nab-paclitaxel appears to be significantly better compared with FOLFIRINOX; however, the survival advantage is not as prolonged as FOLFIRINOX. The last regimen, gemcitabine + erlotinib, is an option; however, in reviewing the data compared with single-agent gemcitabine, the median overall survival difference is small—6.27 months with the combination versus 5.91 months with single-agent gemcitabine.4 However, this regimen appears to have the least toxicity compared to FOLFIRINOX and gemcitabine + nab-paclitaxel. The most common grade 3 or 4 toxicities reported in the gemcitabine + nab-paclitaxel study included fatigue, hematologic adverse events, and neuropathy.  FOLFOX does not have Category 1 designation, and is usually reserved for the second-line setting. Therefore, the optimal treatment option for this patient should factor in the patient’s age, performance status, and personal quality-of-life preferences. Although, this patient has multiple co-morbidities, his age and performance status make him a good candidate for FOLFIRINOX for the first-line setting. In this case, because the patient’s ECOG status has worsened and he is not tolerating FOLFIRINOX, the gemcitabine combination with nab-paclitaxel would be a reasonable alternative treatment. In the MPACT clinical trial of gemcitabine + nab-paclitaxel, patients with lower performance status were included.3 In addition, the gemcitabine + nab-paclitaxel combination is not as emetogenic as FOLFIRINOX, and the hematologic toxicity can be managed via recommended package insert dosage adjustments.

References

  1. National Comprehensive Cancer Network. Clinical Practice Guidelines, 2013. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp
  2. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. New Engl J Med 2011;364: 1817-1825.
  3. Von Hoff DD, Ervin T, Arena FP, et al.  Results of a randomized phase III trial (MPACT) of weekly nab- paclitaxel plus gemcitabine vs gemcitabine alone in patients with metastatic adenocarcinoma. N Engl J Med. 2013;369(18): 1691-1703.4.
  4. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer:  a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(15): 1960-1966.
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