Sequential gemcitabine (G), oxaliplatin (O), and irinotecan (I) based weekly metronomic chemotherapy (MC) regimens for the treatment of metastatic pancreatic cancer (mPC): A community cancer clinic ex
By Ben M. Chue, Bryce D. La Course
Background
Metastatic pancreatic cancer has a poor prognosis with median overall survival ranging from 8.5 to 11.1 months with standard treatment.
The dismal prognosis, lack of new therapy options, and poor tolerability of standard treatment highlight the need for new innovative treatments.
Metronomic chemotherapy regimens utilize lower doses of chemotherapy that are administered more frequently which can maintain dose intensity, increase dose density, all while reducing toxicity and improving quality of life.
Metronomic chemotherapy is thought to have anti-angiogenic, anti-stromal, and immune modulating effects in addition to direct cytotoxic effects.
Table 1. Patient Data
Patient Number
Number of Prior Chemotherapy Treatments
Survival (months) Since Diagnosis
Survival (months) Since Metronomic Chemotherapy
Received PaG, POLF, or PIC/PILF More than Once
1
0
143.7
141.0
Yes
2
2
77.1
72.0
Yes
3
0
61.0
59.2
No
4
2
35.0
13.3
No
5
1
32.1
21.2
No
6
1
31.2
20.3
No
7
2
30.9
14.8
No
8
4
30.1
26.8
Yes
9
0
29.2
28.8
Yes
10
2
27.5
10.5
No
11
0
24.3
23.8
Yes
12
0
23.3
19.5
Yes
13
1
22.3
19.2
Yes
14
0
21.7
21.1
Yes
15
0
19.3
17.6
No
16
0
18.4
14.9
No
17
0
17.3
16.6
Yes
18
3
17.1
4.7
No
19
0
13.8
13.5
Yes
20
1
12.7
4.5
No
21
2
11.9
6.0
No
22
0
9.9
6.5
No
23
0
8.9
7.1
No
24
1
8.6
4.7
No
25
0
6.8
6.0
No
26
1
6.1
3.3
No
27
0
4.9
4.5
No
28
0
4.4
2.8
No
29
1
3.6
0.7
No
30
0
2.0
1.8
No
Methods and Patients
A retrospective analysis of treatment regimens and survival of patients with biopsy-proven metastatic pancreatic cancer who received treatment between August 2004 and August 2018 was performed.
30 patients with biopsy-proven metastatic pancreatic cancer were identified (Table 1). 18 patients were female and 12 were male, with a median age of diagnosis of 63 (range 33 to 77).
Results
Figure 1 Median Overall Survival After Diagnosis
Median overall survival of this cohort was 18.9 months after diagnosis (Figure 1) and 14.2 months after beginning metronomic chemotherapy.
70% of patients (21/30) survived longer than 12 months, 37% (11/30) greater than 24 months, and 27% (8/30) greater than 30 months. 3 patients survived longer than 5 years.
All metronomic chemotherapy regimens (Figure 2) were given on a weekly basis.
16 patients received PaG as their first regimen. 12 of these 16 patients then received POLF as their second regimen, and 7 of these 12 patients subsequently received PIC or PILF as their third regimen.
The 7 patients above had a median overall survival of 21.7 months after diagnosis and 19.1 months after beginning metronomic chemotherapy.
10 patients were successfully able to receive PaG, POLF, or PIC/PILF more than once after first receiving approximately 12 weeks of each regimen.
The 10 patients who received PaG, POLF, or PIC/PILF more than once had a median overall survival of 23.8 months after diagnosis and 22.5 months after beginning metronomic chemotherapy.
Figure 2. Weekly Chemotherapy Regimen Dosing and Duration
Discussion
The combination of chemotherapy agents in the PaG, POLF, and PIC/PILF regimens were chosen by combining chemotherapy agents that are synergistic in their efficacy, but not overly additive in their side effects.
Switching a chemotherapy regimen too soon may be ineffective in treating the disease while waiting too long to switch regimens can result in disease resistance.
Switching chemotherapy regimens before anticipated disease progression may prevent or delay the development of chemotherapy resistance, allowing for regimens to be used again in the future.
Conclusions
Weekly metronomic chemotherapy regimens such as PaG, POLF, and PIC/PILF that are given sequentially are an effective treatment for metastatic pancreatic cancer.
Switching regimens may prevent or delay the development of chemotherapy resistance, allowing for chemotherapy regimens to be used again in the future, potentially allowing for longer survival.
Future Directions
We hope that the exciting results of this study prompt the investigation of the sequential administration of metronomic chemotherapy with the PaG, POLF, and PIC/PILF regimens in larger clinical trials.
If you are interested in collaborating and conducting a clinical trial, please contact us.
