From the Guidelines
The likelihood of treating a stage 4 pancreatic adenocarcinoma in a 60-year-old is generally poor, with a median survival of 6.2 months and a 1-year survival rate of 20% with gemcitabine (GEM) treatment, but can be improved with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) which has shown a median survival of 11.1 months and a 1-year survival rate of 48.4% in patients with good performance status 1.
Treatment Options
- FOLFIRINOX is a novel therapeutic option for patients ≤75 years of age with a good performance status (0 or 1) and a level of bilirubin ≤1.5 ULN, and can be considered as a first-line treatment for stage IV pancreatic cancer 1.
- Gemcitabine (GEM) is a reasonable choice for patients with metastatic disease, but combinations of GEM and other cytotoxic agents do not confer a significant advantage in survival apart from capecitabine 1.
- The combination of GEM and erlotinib can be considered as a treatment option, but treatment with erlotinib is only continued if patients develop skin rash within the first 8 weeks of treatment 1.
Palliative Care
- Palliative care should be integrated early to manage symptoms like pain, jaundice, and digestive issues.
Clinical Trials
- Enrollment of patients with pancreatic cancer in clinical trials for all lines of treatment should be encouraged to further improve the systemic treatment of this disease 1.
Quality of Life
- FOLFIRINOX has been shown to delay deterioration of quality of life, and should be considered as a treatment option for patients with good performance status 1.
From the FDA Drug Label
The efficacy of gemcitabine was evaluated in two trials, (Studies 5 and 6), a randomized, single-blind, two-arm, active-controlled trial (Study 5) conducted in patients with locally advanced or metastatic pancreatic cancer who had received no prior chemotherapy and in a single-arm, open-label, multicenter trial (Study 6) conducted in patients with locally advanced or metastatic pancreatic cancer previously treated with fluorouracil or a fluorouracil-containing regimen
In Study 5, patients were randomized to receive either gemcitabine 1000 mg/m 2intravenously over 30 minutes once weekly for 7 weeks followed by a one-week rest, then once weekly for 3 consecutive weeks every 28-days in subsequent cycles (n=63) or fluorouracil 600 mg/m 2intravenously over 30 minutes once weekly (n=63)
The major efficacy outcome measure in both trials was "clinical benefit response"
Patients treated with gemcitabine had statistically significant increases in clinical benefit response, survival and time to disease progression compared to those randomized to receive fluorouracil.
Table 23: Efficacy Results in Study 5
Efficacy Parameter Gemcitabine (N= 63) Fluorouracil (N= 63) Clinical benefit response 22.2% 4.8% Survival Median (95% CI) in months 5.7 (4.7,6.9) 4.2 (3.1,5. 1) Time to Disease Progression Median (95% CI) in months 2.1 (1.9,3.4) 0.9 (0.9,1.1)
The likelihood of treating a stage 4 pancreatic adenocarcinoma in a 60-year-old with gemcitabine is low to moderate.
- Clinical benefit response was observed in 22.2% of patients treated with gemcitabine in Study 5.
- Median survival was 5.7 months for patients treated with gemcitabine.
- Time to disease progression was 2.1 months for patients treated with gemcitabine. It is essential to note that these results are based on a clinical trial and may not be directly applicable to an individual patient. The decision to treat a patient with gemcitabine should be made on a case-by-case basis, considering the patient's overall health, medical history, and other factors 2.
From the Research
Treatment Options for Stage 4 Pancreatic Adenocarcinoma
The treatment of stage 4 pancreatic adenocarcinoma in a 60-year-old patient is a complex issue, and the likelihood of successful treatment depends on various factors, including the patient's overall health, performance status, and the presence of any comorbidities.
- The management of pancreatic cancer in the elderly population is gaining increasing relevance due to the aging of the population, which will result in a rise in the incidence of pancreatic adenocarcinoma 3.
- The European Society for Medical Oncology (ESMO) guidelines recommend a gemcitabine doublet + nab-paclitaxel (Gem/Nab-P) or a modified FOLFIRINOX regimen (mFOLFIRINOX) as options for systemic chemotherapy in patients with metastatic pancreatic ductal carcinoma (mPDAC) 4.
Chemotherapy Regimens
The choice of chemotherapy regimen depends on various factors, including the patient's performance status, comorbidities, and previous treatments.
- A direct comparison of Gem/Nab-P and mFOLFIRINOX in treatment-naïve mPDAC patients demonstrated significantly longer overall survival (OS) in Gem/Nab-P-treated patients, exceeding 17 months with a lower incidence of non-hematologic toxicity 4.
- The GEMPAX study, a randomized phase III clinical trial, compared the efficacy and tolerability of gemcitabine plus paclitaxel versus gemcitabine alone as second-line treatment for patients with mPDAC, and found that both progression-free survival (PFS) and objective response rate (ORR) were significantly improved in the gemcitabine plus paclitaxel arm 5.
Adjuvant Therapy
Adjuvant therapy is an important aspect of treatment for resected pancreatic ductal adenocarcinoma.
- A randomized, open-label, phase III trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma, and found that the median overall survival (OS) was 41.8 months in the nab-paclitaxel + gemcitabine arm versus 37.7 months in the gemcitabine arm 6.
Challenges and Future Directions
Despite advances in chemotherapy, radiotherapy, and targeted therapies, pancreatic cancer remains a challenging disease to treat, and there is an essential need to increase survival by developing more innovative treatment approaches 7.
- The underrepresentation of older patients in clinical trials is a significant issue, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients 3.