Double-blind randomized study of lonidamine and radiotherapy in head and neck cancer

Magno, L; Terraneo, Fabrizia; Bertoni, F.; Tordiglione, M; Bardelli, D; Rosignoli, Maria Teresa; Ciottoli, G B

doi:10.1016/0360-3016(94)90225-9

Cited by 31 publications

(13 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At least 14 phase II studies with lonidamine either as a single agent or in combination with chemotherapy and radiation have been reported in breast, lung, ovarian, and head and neck cancer. The heterogeneity and uncontrolled design of these studies can only suggest the efficacy of lonidamine [ 36 – 49 ] ( Table 2 ). These data led to testing lonidamine in 5 phase III trials in breast [ 50 – 54 ] and 5 trials in lung cancer [ 55 – 59 ].…”

Section: Lonidaminementioning

confidence: 99%

Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy

Cervantes-Madrid

Romero

Dueñas‐González

2015

BioMed Research International

101

View full text Add to dashboard Cite

Abnormal metabolism is another cancer hallmark. The two most characterized altered metabolic pathways are high rates of glycolysis and glutaminolysis, which are natural targets for cancer therapy. Currently, a number of newer compounds to block glycolysis and glutaminolysis are being developed; nevertheless, lonidamine and 6-diazo-5-oxo-L-norleucine (DON) are two old drugs well characterized as inhibitors of glycolysis and glutaminolysis, respectively, whose clinical development was abandoned years ago when the importance of cancer metabolism was not fully appreciated and clinical trial methodology was less developed. In this review, a PubMed search using the words lonidamine and 6-diazo-5-oxo-L-norleucine (DON) was undertaken to analyse existing information on the preclinical and clinical studies of these drugs for cancer treatment. Data show that they exhibit antitumor effects; besides there is also the suggestion that they are synergistic. We conclude that lonidamine and DON are safe and potentially effective drugs that need to be reevaluated in combination as metabolic therapy of cancer.

show abstract

Section: Lonidaminementioning

confidence: 99%

Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy

Cervantes-Madrid

Romero

Dueñas‐González

2015

BioMed Research International

101

View full text Add to dashboard Cite

show abstract

“…Two clinical trials originating in Italy in the early 1990s evaluated the role of metabolic targeting in HNSCC and suggested that the addition of lonidamine to either external beam radiation or chemotherapy (methotrexate) improved clinical outcomes 72, 73. In the setting of a phase III double‐blind, randomized, placebo‐controlled trial of 97 patients with stage II–IV disease, the addition of lonidamine resulted in a lower treatment‐failure rate (50% vs 77% for placebo), improved locoregional control (63% vs 37% at 5 years), and disease‐free survival (40% vs 19%) 73. With these exceptions, metabolic targeting in HNSCC has been primarily limited to a small number of preclinical studies and focused on 2‐DG.…”

Section: Implications Of Altered Metabolism For Hnscc Response To Thementioning

confidence: 99%

Altered metabolism in head and neck squamous cell carcinoma: an opportunity for identification of novel biomarkers and drug targets

Sandulache

Myers²

2011

Head & Neck

View full text Add to dashboard Cite

Tumor cells were first shown to exhibit a distinct metabolic phenotype over 80 years ago. Since then, it has become clear that multiple oncogenic events contribute to the development of a metabolic phenotype which supports rapid proliferation. Because this phenotype represents an essential component of tumorigenesis and disease progression it also represents a potential source of biomarkers associated with aggressive disease. In addition, the addiction of tumor cells to specific nutrients, and the up-regulation of key metabolic enzymes provide unique opportunities for pharmacologic manipulation. Despite the use of multimodality treatment, survival rates for patients with advanced HNSCC remain low, partially due to the development of drug resistance. In this review, we evaluate the role of altered HNSCC metabolism as both a source of novel biomarkers and a means to bypass resistance mechanisms to conventional forms of therapy.

show abstract

“…In the late 1980s, lonidamine (LND, also known as AF1890), a reversible inhibitor of spermatogenesis [ 72 ], was widely employed in clinical trials for cancer therapy in combination with several anticancer drugs and/or radiation (for a review, see [ 73 ]). LND is characterized by relatively mild side effects that do not overlap with those related to conventional cytostatic therapies [ 74 ]. Its toxicity does not involve bone marrow, but myalgia appears as the most relevant and common side effect [ 74 ], likely related to the proton-linked Monocarboxylate Transporter (MCT) inhibition and consequent lactate accumulation in myocytes.…”

Section: Main Textmentioning

confidence: 99%

“…LND is characterized by relatively mild side effects that do not overlap with those related to conventional cytostatic therapies [ 74 ]. Its toxicity does not involve bone marrow, but myalgia appears as the most relevant and common side effect [ 74 ], likely related to the proton-linked Monocarboxylate Transporter (MCT) inhibition and consequent lactate accumulation in myocytes. In male patients, reversible azoospermia should be taken into account.…”

Section: Main Textmentioning

confidence: 99%

Drug repurposing for the treatment of glioblastoma multiforme

Abbruzzese

Matteoni

Signore

et al. 2017

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundGlioblastoma Multiforme is the deadliest type of brain tumor and is characterized by very poor prognosis with a limited overall survival. Current optimal therapeutic approach has essentially remained unchanged for more than a decade, consisting in maximal surgical resection followed by radiotherapy plus temozolomide.Main bodySuch a dismal patient outcome represents a compelling need for innovative and effective therapeutic approaches. Given the development of new drugs is a process presently characterized by an immense increase in costs and development time, drug repositioning, finding new uses for existing approved drugs or drug repurposing, re-use of old drugs when novel molecular findings make them attractive again, are gaining significance in clinical pharmacology, since it allows faster and less expensive delivery of potentially useful drugs from the bench to the bedside. This is quite evident in glioblastoma, where a number of old drugs is now considered for clinical use, often in association with the first-line therapeutic intervention. Interestingly, most of these medications are, or have been, widely employed for decades in non-neoplastic pathologies without relevant side effects. Now, the refinement of their molecular mechanism(s) of action through up-to-date technologies is paving the way for their use in the therapeutic approach of glioblastoma as well as other cancer types.Short conclusionThe spiraling costs of new antineoplastic drugs and the long time required for them to reach the market demands a profoundly different approach to keep lifesaving therapies affordable for cancer patients. In this context, repurposing can represent a relatively inexpensive, safe and fast approach to glioblastoma treatment. To this end, pros and cons must be accurately considered.

show abstract

Double-blind randomized study of lonidamine and radiotherapy in head and neck cancer

Cited by 31 publications

References 32 publications

Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy

Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy

Altered metabolism in head and neck squamous cell carcinoma: an opportunity for identification of novel biomarkers and drug targets

Drug repurposing for the treatment of glioblastoma multiforme

Contact Info

Product

Resources

About