The most widespread shortage identified in the new survey involves ifosfamide, a generic chemotherapy drug that 94 percent of responding centers reported as being in short supply. Ifosfamide is far from a niche product: it is a workhorse alkylating agent deployed in treatment regimens for bladder, ovarian, testicular, and uterine cancers, as well as soft tissue sarcoma, osteosarcoma, and several adult and pediatric leukemias and lymphomas. Its inclusion among pediatric and adolescent cancer protocols makes the shortage particularly consequential, because clinicians managing young patients with limited therapeutic alternatives have fewer options to substitute when a foundational drug becomes scarce. The breadth of ifosfamide’s use across tumor types means that a single manufacturing failure can touch nearly every subspecialty within a comprehensive cancer center at once, from sarcoma clinics to hematology wards.

Platinum-based chemotherapy agents, which form the backbone of curative and palliative regimens for numerous tumor types, are also under strain once again. Seventy-one percent of surveyed centers reported a current shortage of carboplatin, a striking return of the supply crisis that first drew national attention in 2023, while 16 percent reported shortages of cisplatin. These two drugs are among the most widely used cytotoxic agents in modern medicine, appearing in protocols for lung, ovarian, testicular, head and neck, and many other cancers. In addition, more than half of respondents reported ongoing shortages of Bacillus Calmette-Guérin, or BCG, the immunotherapy instilled directly into the bladder to treat non-muscle-invasive bladder cancer, a therapy for which there is no simple pharmacologic equivalent. The recurrence of carboplatin shortages, after an intense period of public attention and federal response in 2023, suggests that the underlying vulnerabilities in the generic injectable drug supply chain have not been resolved.

NCCN first began surveying its Member Institutions about drug shortages in June 2023, when an abrupt collapse in the supply of carboplatin and cisplatin, traced in part to quality problems at overseas manufacturing facilities, forced oncologists across the country to ration doses and delay treatments. The fact that the network has continued to measure the problem for more than three years provides a rare longitudinal view of a persistent public health failure. When the latest survey asked pharmacy directors whether national or state policies had made the shortage situation better or worse since 2023, only 4 percent said conditions had improved, while 96 percent felt the situation had stayed the same. That near-unanimous assessment of policy stagnation is perhaps the most politically significant finding in the dataset, indicating that legislative and regulatory efforts to date have not yet altered the economic dynamics that produce recurring shortages.

Crystal S. Denlinger, MD, Chief Executive Officer of NCCN, described the persistence of the problem as disheartening, noting that recurring or continued shortages of some drugs have continued despite years of raising the alarm and providing insight about what she characterized as a disruptive and dangerous issue for cancer care in America. Denlinger emphasized that the cancer centers in the network have developed internal strategies, task forces, and communications plans to keep patient care and clinical trials on track. The good news, she noted, is that those mechanisms exist; the bad news is that managing shortages consumes time and attention that could otherwise be spent improving patient experiences and outcomes, and it adds additional stress to an already burdened system. Her comments capture a paradox familiar to hospital pharmacists nationwide: the institutions best equipped to absorb supply shocks are also the ones expending enormous invisible labor to do so.

The operational toll of shortages is quantified elsewhere in the survey. Sixty-one percent of responding centers reported that they required pharmacy and physician-led mitigation strategies to keep all of their patients on a recommended dose and schedule. The majority of those centers implemented waste management strategies, which can include conserving vials, sharing partially used vials across patients under strict sterility protocols, and adjusting compounding practices to extract every usable dose from limited inventory. Others explored alternative recommended regimens, drawing on the NCCN Clinical Practice Guidelines in Oncology to identify evidence-based substitutions that preserve guideline-recommended care when a preferred agent is unavailable. These workarounds are clinically defensible, but they represent a continuous, resource-intensive improvisation that would be unnecessary in a functioning market.

When treatment plans did have to be modified because of shortages, 90 percent of centers reported a need for repeat prior authorization of the revised plan. That administrative requirement significantly increases the amount of work per patient and introduces the potential for delays in care continuity, since insurers must re-approve altered regimens before treatment can proceed. For patients, the consequence can be a gap between the decision to change therapy and the ability to actually receive it, a window in which aggressive cancers do not pause. For clinical staff, prior authorization rework compounds the pharmacy labor already consumed by shortage mitigation, illustrating how a supply chain failure upstream cascades into administrative burden downstream, multiplying the true cost of each shortage far beyond the price of the missing drug itself.

On the question of solutions, the survey revealed a strong consensus among pharmacy leadership. Alyssa Schatz, DrPh, MSW, Vice President of Policy and Advocacy at NCCN, noted that nearly every pharmacy director who responded would like to see economic incentives put in place to encourage high-quality manufacturing for generic cancer medications, something advocates have been requesting for years. One survey respondent summarized the core problem in stark terms: many oncology generics are clinically indispensable but economically unattractive, and without correcting that economic imbalance, shortages are likely to recur. The structural logic is well understood in health policy circles. Generic injectable drugs are cheap, which benefits payers and patients, but rock-bottom prices leave manufacturers with thin margins, little incentive to invest in quality infrastructure or redundancy, and every reason to exit the market when problems arise. The survey also illuminated a desire for better information about generic suppliers and for earlier notifications by manufacturers to the US Food and Drug Administration, which would give hospitals more lead time to prepare mitigation plans before shelves empty.

NCCN is part of the End Cancer Drug Shortages Coalition, a group that brings together more than a dozen hematology and oncology nonprofits to address the issue and propose long-term solutions. In May 2026, the coalition issued a consensus statement offering a big-picture assessment of the ongoing problem and a list of policy proposals for the future, ranging from payment and purchasing reforms to manufacturing quality incentives. The coalition’s work reflects a growing recognition among oncology professional societies that shortage response cannot remain the province of individual hospital task forces indefinitely, and that durable fixes must operate at the level of the market itself, where the pricing of essential generic medicines currently fails to reward reliability.

For patients and clinicians, the practical meaning of the 2026 survey is sobering: three years of advocacy, congressional hearings, and federal attention have produced internal resilience but not external change. Every comprehensive cancer center surveyed is still managing around at least one missing chemotherapy agent, and a substantial fraction is juggling five or more at once. The network’s findings, available through NCCN’s drug shortage resources, will continue to serve as a benchmark for measuring whether the economic incentives, supplier transparency measures, and early notification requirements that pharmacy leaders overwhelmingly support are eventually translated into policy. Until then, the quiet work of vial conservation, regimen substitution, and reauthorization paperwork will remain an unheralded but essential layer of cancer care in the United States, holding the system together one shortage at a time.

Subject of Research: Persistent generic cancer medication shortages reported by United States comprehensive cancer centers

Article Title: New NCCN survey highlights persistent cancer medication shortages across United States

Article References: New NCCN survey highlights persistent cancer medication shortages across United States. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: NCCN, drug shortages, cancer medication, ifosfamide, carboplatin, cisplatin, BCG, generic drugs, oncology, pharmacy, health policy, supply chain

The research, led by Liang-rui Qin and Can Hu of the State Key Laboratory of Ultrasound in Medicine and Engineering at Chongqing Medical University, together with colleagues including corresponding authors Yong-hong Du and Dai-rong Li, focused on a deceptively straightforward therapeutic idea: deliver oxygen-generating capacity directly into the granuloma microenvironment. Catalase is an enzyme that breaks down hydrogen peroxide into water and molecular oxygen. By injecting catalase locally into tuberculous granulomas at defined stages of infection, the team hoped to relieve the hypoxia, the severe oxygen depletion, that characterizes these lesions and that has long been suspected of undermining both immune function and drug efficacy.

To test the concept, the researchers established a murine subcutaneous tuberculous granuloma model using Bacillus Calmette-Guérin, or BCG, the attenuated mycobacterial strain best known as the tuberculosis vaccine. Mice were divided into treatment groups receiving either catalase, cobalt chloride, a chemical that mimics hypoxia, or a saline control. Crucially, the interventions were timed: one group received treatment at day six after infection, representing an early stage of granuloma formation, while another received it at day twelve, when lesions were more established. The team then assessed outcomes using a battery of techniques including histopathology, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assays, and lipidomics, an analytical approach that profiles the full repertoire of lipid species in tissue.

The baseline findings were sobering. As BCG infection progressed, the granulomas became progressively more hypoxic, and this deterioration was accompanied by vascular dysfunction, visible as reduced expression of CD31, a marker of endothelial cells, and alpha-smooth muscle actin, a marker of vascular mural cells. Collagen deposition increased, scarring the lesions and further restricting blood flow. Lipid accumulated within the tissue, and bacterial load, measured as colony-forming units, climbed in parallel. In other words, the granuloma behaves like a self-reinforcing vicious cycle: poor vasculature starves the tissue of oxygen, hypoxia damages vessels further and promotes fibrosis and fat buildup, and the worsening microenvironment favors bacterial persistence.

Against this backdrop, the results of early catalase intervention stood out sharply. When catalase was administered at day six, the treatment downregulated hypoxia inducible factor-1 alpha, the master molecular switch that cells activate under low oxygen, along with vascular endothelial growth factor, a signaling protein that hypoxic tissues produce to stimulate new but often dysfunctional blood vessel growth. With the hypoxic burden lifted, the vascular structure inside the granulomas improved, as did vessel permeability, potentially opening a window for drugs that would otherwise fail to reach the bacteria. Collagen and lipid deposition both declined, indicating that the fibrotic and metabolic deterioration of the lesion had been blunted.

Perhaps the most technically intriguing finding came from the lipidomics analysis. Early catalase treatment did not simply reduce lipid accumulation indiscriminately; it specifically reshaped the lipid profile of the granuloma. The phospholipid species phosphatidylserine 18:0/18:0 was downregulated, while multiple subtypes of phosphatidylinositol and phosphatidylethanolamine were upregulated. This specificity matters because mycobacteria are notorious lipid manipulators: they co-opt host lipid metabolism to build their own protective niches inside macrophages, and aberrant lipid handling within granulomas has been linked to bacterial persistence and lesion necrosis. The finding suggests that oxygen restoration does not merely improve tissue plumbing but actively recalibrates the metabolic landscape on which the bacteria depend.

Timing, however, proved to be everything. When catalase was given at day twelve, well after the granulomas had matured, the therapeutic benefit was markedly limited. The late-stage lesions, already entrenched in hypoxia, fibrosis, and lipid dysregulation, apparently could not be rescued by a single round of oxygen-generating enzyme therapy. Conversely, when the researchers injected cobalt chloride to chemically induce hypoxia, every pathological measure worsened: vascular markers fell further, collagen and lipid deposition increased, and the lesions deteriorated across the board. This reciprocal experiment strengthens the causal argument that hypoxia is not merely correlated with granuloma progression but actively drives it.

The implications for tuberculosis therapy are potentially significant. Current drug regimens for tuberculosis require months of multidrug therapy, and treatment failure is often attributed to poor drug penetration and the metabolically dormant state that bacteria adopt in hypoxic lesions. If restoring oxygenation can normalize granuloma vasculature and reverse the metabolic conditions that shelter persistent bacteria, catalase-based local oxygen therapy could, in principle, serve as an adjunct that makes existing antibiotics work better, rather than a replacement for them. The study’s authors note that their findings suggest a potential application prospect in animal models that more closely recapitulate human tuberculosis, an important caveat, since the subcutaneous BCG model, while tractable and ethically manageable, differs in key respects from pulmonary infection with virulent M. tuberculosis in humans.

Those caveats deserve emphasis. BCG is an attenuated organism, and the granulomas in this model form in the skin rather than the lung, where the architecture of human tuberculous lesions, including caseous necrosis and cavitation, presents additional barriers. The dosing, delivery route, and safety profile of local catalase administration would all need to be established in more faithful models before any translation toward patients could be contemplated. Nonetheless, the study offers a mechanistically grounded proof of concept that the pathological microenvironment of a granuloma is a druggable target in its own right, and that the window for intervening is early, before fibrosis and lipid derangement become irreversible.

What makes the work resonate beyond tuberculosis is its broader message about infectious disease: the battlefield matters as much as the combatants. Rather than attacking the bacteria directly, this approach remodels the tissue ecosystem in which the bacteria survive, targeting hypoxia signaling, vascular integrity, and lipid metabolism simultaneously. As researchers increasingly recognize that chronic infections are sustained by microenvironmental niches, strategies that restore normal tissue physiology, whether through oxygen-generating enzymes, vascular repair, or metabolic modulation, may complement the antibiotic arsenal in ways that new drugs alone cannot. For a disease that still kills well over a million people each year, even a modest improvement in drug penetration and bacterial clearance inside granulomas could translate into shorter cures and fewer treatment failures. The Chongqing team’s catalase experiments are an early step, but they point toward a reframing of tuberculosis therapy: treat the lesion, not just the microbe.

Subject of Research: Catalase-based local oxygen therapy targeting hypoxia and lipid metabolism in tuberculous granulomas

Article Title: Therapeutic effects of early catalase intervention in tuberculous granulomas: targeting hypoxia and lipid dysregulation

Article References: Therapeutic effects of early catalase intervention in tuberculous granulomas: targeting hypoxia and lipid dysregulation. (n.d.). https://doi.org/10.1186/s12879-026-14516-8

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14516-8

Keywords: tuberculosis, granuloma, catalase, hypoxia, HIF-1alpha, oxygen therapy, BCG, lipidomics, vascular dysfunction, fibrosis, mouse model, BMC Infectious Diseases