Off-label drugs for cancer Recovery and Survival

Off-label drugs are medicines that are approved for one condition but may also be studied or used in cancer care for a different purpose, cancer type, dose, or treatment setting. For example, Metformin was originally approved to treat 2 diabetes but is also used off-label to treat cancer.

Some off-label drugs are being investigated because they may affect cancer-related pathways such as inflammation, metabolism, blood clotting, immune activity, tumour signalling, or resistance to treatment. This page explores selected off-label drugs with scientific or clinical interest in cancer.

The National Cancer Institute notes that off-label use is common in cancer care, partly because cancer drugs may work across more than one cancer type and because combination regimens often include drugs used outside their labelled indication.

Off-label drugs for cancer

Here are some off-label drugs that have shown efficacy in cancer treatment.

Bisphosphonates (anti-hypercalcemia drugs)

This study involving 18 766 women with early breast cancer, says:
…When the study authors looked at the findings according to the trial participants’ menopausal status, they found that treatment with adjuvant bisphosphonates had no effect on any of the outcomes for premenopausal women. However, among the 11,767 postmenopausal women included in the analysis, the use of bisphosphonates was associated with statistically significant reductions in distant recurrence, in bone recurrence, and in death from breast cancer.

Dipyridamole

According to Institute of Integrative BioOncology, Dipyridamole is a widely prescribed drug used in treating heart problems caused by narrowed heart arteries. Dipyridamole is similar to aspirin, an antiplatelet drug that limits platelet adhesion. In addition, this medication has few side effects. Therefore it is safe to use.

Dipyridamole increases the concentration of anticancer drugs in cancer cells like

• 5-fluorouracil (5-FU), 
• Piperidine
• Methotrexate
• Vincristine

Brand Name: Persantine

An article published on the Johns Hopkins Medicine website says Timothy F. Osborne, Ph.D., director of the Institute for Fundamental Biomedical Research, and his colleagues may have found a way to interfere with certain biological pathways to deprive some cancer tumors of the fats upon which they thrive, by repurposing a drug used to prevent blood clots.

In their recent study, published in the Feb. 18, 2021 issue of the prestigious peer-reviewed scientific journal Cell Chemical Biology, Osborne and colleagues describe how the drug dipyridamole, a previously developed drug aimed at thinning the blood to prevent blood clots after some types of heart surgery, can be “repurposed” to inhibit an unrelated specific biological pathway to “starve” certain cancers, such as pancreatic cancer, prostate cancer, colorectal cancer, breast cancer and liver cancer, by denying them the fats on which they depend for growth.

Disulfiram

This 2024 study says Disulfiram (DSF) has been used since 1951 and is well tolerated with minimal side effects. Several studies show the antitumor effects of DSF, particularly the combination of DSF and copper (DSF/Cu), on a wide range of cancers such as glioblastoma (GBM), breast cancer, liver cancer, pancreatic cancer, and melanoma.

DSF, especially DSF/Cu, shows high anti-tumor effects on diverse cancers, which is associated with induction of the intracellular ROS, inhibition of proteasome activity, as well as inhibition of nuclear factor-kappa B (NF-κB) signaling. In addition, DSF or DSF/Cu targets CSCs and improves radio/chemo-sensitivity, which will provide a novel avenue for cancer treatment in the future.

Doxycycline

This study says doxycycline is an excellent example of how existing, inexpensive, well-tolerated drug might be extended to use as new cancer therapeutic agent (Off-label).
According to the different mechanisms of action of doxycycline, the anti-MMPs effect, its action as DNA-PK inhibitor, its cytotoxic effect on malignant cells and its sensitization of some types of cancer cells for radiation therapy, all give us a promising treatment for different type of cancers such as breast cancer, glioblastoma, leukemia and others.

Niclosamide

Niclosamide belongs to the family of medicines called anthelmintics. Anthelmintics are medicines used in the treatment of worm infections.

Study: In conclusion, the present study offered new ideas for the treatment of chemoresistant HER2-positive breast cancer…Niclosamide combined with cisplatin may be considered as a novel treatment therapy for chemoresistant HER2-positive breast cancer.

Niclosamide, has been repurposed for cancer treatment due to its ability to disrupt multiple oncogenic signaling networks, such as Wnt/β-catenin, NF-κB and STAT3, all of which has fundamental roles in the survival, proliferation, and invasiveness and metastasis of tumors. (study)

Therefore, niclosamide holds great potential for the treatment of cancers and our present study provides strong support for its use in the treatment of TNBC. (study).

Mifepristone

This study of 34 ovarian cancer patients treated with Mifepristone says: Nine (26.5%) of these patients had a response to Mifepristone. Three (9%) patients had a complete response, and six (17.5%), a partial response…Laboratory studies show that Mifepristone can target cancer stem cells. Conclusion: Mifepristone has activity against ovarian cancer resistant to cisplatin and paclitaxel. The drug is well tolerated.

This study says: In summary, we have shown that mifepristone is a potent blocker of ovarian cancer growth in vitro and in vivo. The feasibility of using mifepristone to enhance the efficacy of conventional chemotherapy for ovarian cancer is encouraging and requires further investigation.

Case Report: Long-term high-quality survival following mifepristone treatment with a progesterone receptor antagonist in two cases of advanced metastatic cancer [ a moribund woman with never-treated metastatic lung cancer and a male with bilateral renal cell carcinoma.] These cases helped influence the US Food and Drug Association in granting an investigator-initiated investigational new drug study on advanced non-small cell lung cancer.

Nitazoxanide (NTZ) – anti-parasite drug

Source: Labiotech.eu
A widely used anti-parasite drug, nitazoxanide (NTZ), is able to break down a protein called beta-catenin, which is found at high levels in prostate and colon cancer cells and supports their growth and survival. This opens up the possibility of repurposing the drug for the treatment of these cancers.

This 2023 study concluded:
NTZ is a potential therapeutic agent for bone metastasis induced by the TGF-β/Ac-KLF5 signaling axis in prostate cancer and likely other cancers.

PDE5 inhibitors (Tadalafil, Sildenafil)

This study involving 32 patients with Head and Neck Squamous Cell Carcinoma concluded: These findings demonstrate that tadalafil [Cialis] augments general and tumor-specific immunity in patients with HNSCC and has therapeutic potential in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor-specific immunity is a significant feature of head and neck cancer development. This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor-specific immune suppression in patients with head and neck cancer, with potential for therapeutic application.

This Review says Sildenafil [Viagra] has demonstrated its ability in enhancing anticancer drug delivery through the EPR effect, prompting significant elevation of intratumoral drug concentrations and subsequent cellular death. In addition, sildenafil has demonstrated its implication in the modulation and potentiation of chemotherapeutic agents in a range of different types of cancer. 

This study concluded: A broad range of data, pre-clinical and clinical, has been summarised and presented to make the case that the commercially available and widely used PDE5 inhibitors sildenafil, vardenafil and tadalafil are very strong candidates for repurposing as anticancer agents. These low-cost, low-toxicity drugs show potential to be included with current and emerging standard of care treatments in oncology. The combination with immune checkpoint inhibitors or possible use as perioperative therapies are particularly compelling strategies with the potential to positively improve survival outcomes in a relatively short time-frame.

GLP-1 Agonists

This article posted on the American Society of Clinical Oncology (ASCO) website says:
GLP-1RA exposure demonstrated reduced metastatic progression across 6/7 malignancies, with statistically significant reductions in four cancer types: NSCLC, breast, CRC, and HCC . No significant safety signals or increased adverse events were observed in GLP-1RA-exposed patients compared to controls. Additionally, high tumor GLP-1R expression correlated with improved survival across the seven tumors, most notably in breast cancer . Conclusions: In this large propensity-matched cohort, GLP-1RA initiation after cancer diagnosis was associated with dramatically reduced metastatic progression across multiple solid tumors. Corroborating these clinical findings, elevated GLP-1R expression independently predicted improved overall survival.

Heparin

This study says: Heparin is frequently used in the treatment of cancer-associated thromboembolism. Accumulating clinical evidence indicates that cancer patients treated with unfractionated and low-molecular weight heparin (LMWH) survive longer than patients treated by other anticoagulants, especially patients in the early stage of the disease. Experimental analysis from a number of animal models constantly provides evidence for the ability of heparin to attenuate metastasis. The non-anticoagulant activity of heparin on metastasis includes the ability to inhibit cell-cell-interaction through blocking of P- and L-selectin, to inhibit extracellular matrix protease heparanase, and to inhibit angiogenesis.

This Review says: Several heparin mimetics are showing promise in cancer treatment. Various studies using mimetics alone or in combination with chemotherapy have been conducted and have yielded mixed results. They work on multiple target molecules, mostly receptors such as fibroblast growth factor and endothelial growth factor. The main types of cancers targeted by these drugs are multiple myeloma, pancreatic cancer, hepatocellular carcinoma (HCC), and other solid tumors.

Propranolol

This study says: Propranolol was also shown to have an effect on metastasis to the brain – the other major site of interest in breast cancer. Choy et al assessed retrospective data that showed that for stage II breast cancer patients beta-blocker usage was associated with a significantly reduced risk of post-operative recurrence or distant metastasis…The recent studies outlined in this paper add to the weight of evidence to support the use of propranolol as an anti-metastatic agent in breast cancer.

This study says: We conducted a prospective study in patients with melanoma treated with propranolol for off-label use. After adjusting for known prognostic factors, Cox models confirmed that use of propranolol at the time of diagnosis was significantly inversely associated with recurrence of melanoma with approximately an 80% risk reduction for propranolol users.

This Review says: Thirty-one studies were included, consisting of 7 RCTs, 4 systematic reviews and 20 meta-analyses. The evidence suggests that propranolol may improve cancer outcomes, especially when administered perioperatively, by reducing recurrence risk. However, the results remain inconclusive regarding its use in combination with chemotherapy or radiotherapy, as studies showed mixed results. The timing of propranolol administration, alongside its combination with other cancer therapies, appears to be a key factor in its effectiveness.

Recommended Reading:
Metabolic Drugs for Cancer by Amanda King and Dr Hari Kuhan 
How to Starve Cancer by Jane McLelland 

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Page updated February 2026