MDACT: A New Principle of Adjunctive Cancer Treatment Using Combinations of Multiple Repurposed Drugs, with an Example Regimen.

In part one of this two-part paper, we present eight principles that we believe must be considered for more effective treatment of the currently incurable cancers. These are addressed by multidrug adjunctive cancer treatment (MDACT), which uses multiple repurposed non-oncology drugs, not primarily to kill malignant cells, but rather to reduce the malignant cells' growth drives. Previous multidrug regimens have used MDACT principles, e.g., the CUSP9v3 glioblastoma treatment. MDACT is an amalgam of (1) the principle that to be effective in stopping a chain of events leading to an undesired outcome, one must break more than one link; (2) the principle of Palmer et al. of achieving fractional cancer cell killing via multiple drugs with independent mechanisms of action; (3) the principle of shaping versus decisive operations, both being required for successful cancer treatment; (4) an idea adapted from Chow et al., of using multiple cytotoxic medicines at low doses; (5) the idea behind CUSP9v3, using many non-oncology CNS-penetrant drugs from general medical practice, repurposed to block tumor survival paths; (6) the concept from chess that every move creates weaknesses and strengths; (7) the principle of mass-by adding force to a given effort, the chances of achieving the goal increase; and (8) the principle of blocking parallel signaling pathways. Part two gives an example MDACT regimen, gMDACT, which uses six repurposed drugs-celecoxib, dapsone, disulfiram, itraconazole, pyrimethamine, and telmisartan-to interfere with growth-driving elements common to cholangiocarcinoma, colon adenocarcinoma, glioblastoma, and non-small-cell lung cancer. gMDACT is another example of-not a replacement for-previous multidrug regimens already in clinical use, such as CUSP9v3. MDACT regimens are designed as adjuvants to be used with cytotoxic drugs.

Transdermal fentanyl to parenteral morphine route switch and drug rotation in refractory cancer cachexia.

It is recommended not to use transdermal fentanyl (Fe) patches (TFP) in cancer cachexia but TFP may be the only available option for pain. Limited evidence suggests lower Fe absorption from TFP in cachexia. We describe a case of metastatic breast cancer with refractory cachexia. Her pain was uncontrolled on TFP and was route switched and drug rotated to intravenous morphine (M). We were conservative and did not use the 1:100 TFP to oral M conversion ratio. Assuming opioid needs were similar before and after switch/rotation, the suitable conversion ratio in this case was about 1:25. Absent clear guidelines on converting from TFP in cachexia, it is better to avoid TFP. When essential to use TFP in cachexia, caution should be taken when switching from TFP to avoid overdose.

Caregiver burden among family caregivers of incurable cancer patients in two eastern Mediterranean countries.

BACKGROUND: Although family caregivers (FCs) play an important role in the care provided to incurable cancer patients in our region, little is known about the burden they experience. This study was conducted to determine the prevalence of caregiver burden (CB) among FCs of incurable cancer patients in two Eastern Mediterranean countries and to identify factors that may be associated with significant CB. METHODS: The study included 218 FCs, 165 from Egypt and 53 from Saudi Arabia. The 22-item Zarit Burden Interview (ZBI-22) was used to assess caregiver burden CB. Significant CB was defined as a ZBI-22 score ≥ 21. The assistance with basic ADLs was classified into 3 levels according to FCs' assistance with early/middle/late-loss basic ADLs. The relationship between CB and the assistance with ADLs and other factors was studied. RESULTS: The mean (SD) ZBI-22 score among FCs was 23.4 (9.3) and the majority (128/218, 59%) had significant CB. Eighty-nine percent of FCs assisted with at least one basic ADL. Assistance with late-loss basic ADLs, best supportive care treatment plan and poorer performance status were associated with higher CB (p < 0.0001, =0.018 and = 0.005). However, in logistic regression analysis, only assistance with late-loss ADLs was independently associated with significant CB (OR = 3.4 [95%CI:1.2-9.7], p = 0.024). CONCLUSION: A substantial proportion of FCs of incurable cancer patients in our region experience significant CB. Family caregivers assisting with late-loss basic ADLs are at risk of significant CB and should be routinely screened for CB.