Successful management of doxorubicin overdose and extravasation in a dog with lymphoma.

A dog was hospitalized after accidental overdose and extravasation of doxorubicin. With supportive care and dexrazoxane, systemic toxicity resolved by Day 9 and extravasation injury by Day 36. This case demonstrates that, with treatment, dogs can survive doxorubicin overdose and extravasation. The report also highlights the importance of checking the dose of chemotherapeutic agents and preventing extravasation.

Gestion réussie d'une surdose à la doxorubicine et de l'extravasation chez un chien atteint d'un lymphome. Un chien a été hospitalisé après une surdose accidentelle et l'extravasation de doxorubicine. Avec des soins de soutien et de la dexrazoxane, la toxicité systémique s'est résorbée au Jour 9 et la blessure d'extravasation au Jour 36. Ce cas démontre que, avec un traitement, les chiens peuvent survivre à une surdose de doxorubicine et à l'extravasation. Ce rapport souligne aussi l'importance de la vérification de la dose d'agents chimiothérapeutiques et de la prévention de l'extravasation.(Traduit par Isabelle Vallières).

Safe and effective treatment of spontaneous neoplasms with interleukin 12 electro-chemo-gene therapy.

Electroporation improves the anti-tumour efficacy of chemotherapeutic and gene therapies. Combining electroporation-mediated chemotherapeutics with interleukin 12 (IL-12) plasmid DNA produces a strong yet safe anti-tumour effect for treating primary and refractory tumours. A previously published report demonstrated the efficacy of a single cycle of IL-12 plasmid DNA and bleomycin in canines, and, similarly, this study further demonstrates the safety and efficacy of repeated cycles of chemotherapy plus IL-12 gene therapy for long-term management of aggressive tumours. Thirteen canine patients were enrolled in this study and received multiple cycles of electro-chemo-gene therapy (ECGT) with IL-12 pDNA and either bleomycin or gemcitabine. ECGT treatments are very effective for inducing tumour regression via an antitumour immune response in all tested histotypes except for sarcomas, and these treatments can quickly eradicate or debulk large squamous cell carcinomas. The versatility of ECGT allows for response-based modifications which can overcome treatment resistance for affecting refractory lesions. Importantly, not a single severe adverse event was noted even in animals receiving the highest doses of chemotherapeutics and IL12 pDNA over multiple treatment cycles. This report highlights the safety, efficacy and versatility of this treatment strategy. The data reveal the importance of inducing a strong anti-tumour response for successfully affecting not only the treated tumours, but also non-treated metastatic tumours. ECGT with IL12 pDNA plus chemotherapy is an effective strategy for treating multiple types of spontaneous cancers including large, refractory and multiple tumour burdens.

Safety and efficacy of tumor-targeted interleukin 12 gene therapy in treated and non-treated, metastatic lesions.

The ability to control the immune system to actively attack tumor tissues will be a marvelous weapon to combat the persistent attack of cancer. Unfortunately, safe and effective methods to gain this control are not yet available as cancer therapies. To overcome the impediments to this control, tumor-targeted (tt) Interleukin 12 (IL-12) plasmid DNA can be safely delivered to accessible tumors, and these treatments can induce antitumor immune responses in both the treated and untreated tumors. Here, electroporationmediated ttIL-12 pDNA treatments are shown to be safe and well tolerated in a dose escalation study in canines bearing naturally-occurring neoplasms. The final patient in the dose-escalation study received up to 3,800 µg pDNA distributed among five separate squamous cell carcinoma tumors in doses equivalent to those administered in a Phase I trial with wildtype IL-12 pDNA. Not a single severe adverse event occurred in any patient at any of the five dose levels, and only minor, transient changes were noted in any tested parameter. Clinical response analysis and immune marker mRNA detection of treated and non-treated lesions suggest that ttIL-12 pDNA treatments in only a few tumors can elicit antitumor immune responses in the treated lesions as well as distant metastatic lesions. These observations and results demonstrate that ttIL-12 pDNA can be safely administered at clinical levels, and these treatments can affect both treated and nontreated, metastatic lesions.