Intratumoral Bleomycin Research Articles

Comparison of Three Chemotherapy Protocols With Electrochemotherapy for the Treatment of Feline Cutaneous Squamous Cell Carcinoma.

Electrochemotherapy (ECT) with intravenous (IV) and/or intratumoral (IT) bleomycin has shown considerable efficacy in the treatment of non-resectable feline cutaneous squamous cell carcinoma (cSCC), boasting response rates of up to 95%, but other chemotherapy protocols have not yet been investigated. The objective of this prospective multicentre study was to compare the overall response rate (ORR) and progression-free interval (PFI) between cats with cSCC treated with ECT using IT and IV carboplatin (IV + IT), IV carboplatin (IV) or IV bleomycin (IV). A total of 44 cats with unresectable cSCC across three centres were enrolled and treated with ECT using carboplatin IV + IT (n = 10), carboplatin IV (n = 11) or bleomycin IV (n = 23). Treatment response according to RECIST criteria was recorded at 2 and 4 weeks post-treatment, and patients were followed until disease progression and/or death. All three groups were comparable regarding age, sex, weight, and lesion size. Adverse events were generally mild, localised and similar between groups. ORRs were 90.0% (carboplatin IV + IT), 90.9% (carboplatin IV) and 95.6% (bleomycin IV) and were not significantly different (p = 0.79). Median PFI was not reached for carboplatin IV + IT or carboplatin IV and was 566 days for bleomycin IV, with no significant difference between the three groups (p = 0.81). This study suggests that ECT using IV or IV + IT carboplatin is a reasonable alternative therapeutic option for managing cSCC, and further studies are warranted to compare outcomes between treatment protocols.

Impact of electrochemotherapy in metastatic cutaneous melanoma: a contemporary systematic review and meta-analysis

Background Electrochemotherapy (ECT) harnesses electric pulses to enhance cytotoxic drug delivery into tumors and has entered the armamentarium to treat superficially metastatic melanoma. We performed a systematic review and meta-analysis to assess treatment patterns and patient outcomes. Methods PubMed, Medline, Embase, and the Cochrane Library databases were queried for publication from inception to September 2020. Primary outcome measures were overall and complete response rate (ORR and CRR); secondary outcomes included local control rate (LCR) and overall survival (OS). Results Twenty-seven studies met the selection criteria for a total of 1161 individuals (mean age 71 years) and 5308 tumors (weighted mean size 14 mm). The majority of patients (n = 1124) underwent bleomycin-ECT. Aggregate ORR was 77.6% (95% confidence interval [CI] 71.0 − 83.2%) and CRR 48% (95% CI 42 − 54%), with no significant difference between the route of bleomycin administration (ORR, 69.2 vs. 81.9% following intravenous or intratumoral bleomycin, p = .37) and tumor size (p = .69). When reported (n = 8 studies), 1- and 2-year LCR ranged from 54 to 89% and 72 to 74%, respectively, and 1-year OS (n = 3 studies) from 67 to 89%. Conclusions ECT with either intratumoral or intravenous bleomycin confers a high therapeutic response in cutaneous metastatic melanoma. Moderate evidence supports its low toxicity and durability of local control. Highlights Electrochemotherapy (ECT) is associated with a 77% overall response rate (ORR). Intravenous and intratumoral bleomycin are equally effective. There are no relevant toxicity concerns. One-year local tumor control rate ranges from 54 to 89%. Current literature has significant variation in reporting.

Bleomycin Concentration in Patients’ Plasma and Tumors after Electrochemotherapy. A Study from InspECT Group

The plasma concentration profile of bleomycin in the distribution phase of patients younger than 65 years is needed to determine the suitable time interval for efficient application of electric pulses during electrochemotherapy. Additionally, bleomycin concentrations in the treated tumors for effective tumor response are not known. In this study, the pharmacokinetic profile of bleomycin in the distribution phase in 12 patients younger than 65 years was determined. In 17 patients, the intratumoral bleomycin concentration was determined before the application of electric pulses. In younger patients, the pharmacokinetics of intravenously injected bleomycin demonstrated a faster plasma clearance rate than that in patients older than 65 years. This outcome might indicate that the lowering of the standard bleomycin dose of 15,000 IU/m2 with intravenous bleomycin injection for electrochemotherapy is not recommended in younger patients. Based on the plasma concentration data gathered, a time interval for electrochemotherapy of 5–15 min after bleomycin injection was determined. The median bleomycin concentration in tumors 8 min after bleomycin injection, at the time of electroporation, was 170 ng/g. Based on collected data, the reduction of the bleomycin dose is not recommended in younger patients; however, a shortened time interval for application of electric pulses in electrochemotherapy to 5–15 min after intravenous bleomycin injection should be considered.

The role of electrochemotherapy with intratumoral bleomycin for early tongue carcinoma

Background The role of electrochemotherapy (ECT) using intratumoral bleomycin and electroporation as a first line treatment for oral tongue carcinoma has not been defined. Aims/Objectives To evaluate the method of ECT in oral tongue carcinoma. Material and Methods Twenty-one successive patients with primary T1-T2 oral cancer predominantly of the oral tongue underwent either ECT (test; n = 9), or standard surgical resection and reconstruction (control; n = 12). Outcome variables were: local recurrence rates, 10-year-survival, adverse events, treatment cost, and quality of life. Results The 10-year local recurrence rate (44.4%) was higher and the tumour-specific survival rate (55.6%) was lower in the ECT group compared to the control group (17% and 91.6%, respectively). Postoperative haemorrhage, dysphagia, and pain were more frequent in ECT patients, treatment time was shorter, but treatment cost was higher. Quality of life was not improved by ECT. Conclusions and Significance Our results indicate that ECT seems not as suitable for the treatment of early tongue cancer as it is for neoplastic and metastatic skin lesions and less favourable than standard surgical therapy.

Abstract B33: Immuno gene therapy with IL-12 combined with electrochemotherapy for the treatment of skin and oral tumors in client-owned dogs

Abstract Cancer is a common disease of client-owned dogs, with the majority of solid tumors located in the skin or oral cavity. One of the local ablative therapy is electrochemotherapy, where cytotoxic drugs, bleomycin or cisplatin, are introduced into the cells by application of electric pulses (electroporation). In veterinary oncology, electrochemotherapy proved to be an effective and safe local treatment of tumors in horses, cats, dogs, and exotic animals, where success is comparable to standard surgical therapy. The drawback of electrochemotherapy is that, despite its high local effectiveness, it does not have systemic antitumor effects. In preclinical and some clinical studies, gene electrotransfer (GET) of plasmid encoding IL-12 was effective local therapy eliciting also systemic immune response. By means of electroporation, the plasmid DNA is introduced into the cells, resulting in IL-12 expression. The aim of our study was to evaluate a combination of electrochemotherapy and GET of plasmid encoding canine IL-12 for the treatment of skin and oral tumors in dogs. From June 2015 till October 2018, 51 dogs were enrolled in the clinical study: 38 dogs with 68 skin tumors and 13 dogs with oral tumors. Under general anesthesia, electrochemotherapy and gene therapy with IL-12 were performed. For electrochemotherapy cytotoxic drugs were first administered: bleomycin intravenously or intratumorally or cisplatin intratumorally. Standard electrochemotherapy pulses (8 electric pulses, 100 μs, 1300 V/cm, 5 kHz) were applied 10 minutes after intravenous bleomycin administration and immediately after intratumoral bleomycin or cisplatin administration. After electrochemotherapy, the plasmid pCMVcaIL-12 was applied peritumorally at two sites of the tumor and immediately after application of plasmid DNA the electric pulses were applied, using noninvasive electrodes with 7 pins arranged in hexagonal arrays with central pin (24 pulses, 60 V, 150 ms, 0.40/1.39 Hz). The results of our study showed that the combination of electrochemotherapy and gene therapy of plasmid IL-12 is the most effective in treatment of skin tumors, especially in the case of mast cell tumors, with ~90% of local tumor control rate. Moreover, in the case of skin tumors we demonstrated an effect in distant untreated tumors in 5 dogs, which confirms the systemic (abscopal) effect of the therapy. In the treatment of oral tumors, we achieved 54% of objective local tumor response 1 month after treatment. Although progressive disease occurred in 11/13 patients at the end of observation period, a mean survival time of 7 months was obtained, which is comparable with standard surgical therapy, but without cosmetic or functional shortcomings that occur after surgical treatment. To conclude, the results of our study showed significant antitumor response of combined therapy in the case of skin tumors. Also, for dogs with oral tumors combined therapy represents a valuable treatment option, especially when other treatment approaches are not applicable or acceptable. Citation Format: Maja Cemazar, Ursa Lampreht Tratar, Nina Milevoj, Andreja Brozic, Ana Nemec, Gregor Sersa, Natasa Tozon. Immuno gene therapy with IL-12 combined with electrochemotherapy for the treatment of skin and oral tumors in client-owned dogs [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B33.

Long-term follow-up in patients treated with electrochemotherapy for non-melanoma skin cancer in the head and neck area

Background: Electrochemotherapy (ECT) is a cancer treatment modality where the intracellular accumulation of chemotherapeutic agents is enhanced by an applied electrical field.Aims/Objectives: To evaluate the long-term efficacy, safety and functional outcome after ECT treatment in high-risk non-melanoma skin cancer (NMSC) with curative intent.Materials and methods: Seven patients with SCC or BCC in the head and neck area were treated with ECT with intratumoral bleomycin administration.Results: Five patients were cured by ECT as a mono-modality treatment after a median 10-year follow-up period. Two patients had recurrences and/or persisting tumors after treatment that required salvage surgery and radiotherapy. In two patients, the eye was spared with no visual impairment. In another patient, full facial nerve function was spared.Conclusions: ECT can be a curative as well as an organ and function-sparing mono modality treatment in high-risk NMSC.Significance: Today ECT is mostly used as a palliative treatment. Its curative potential should be further investigated. Randomized studies comparing ECT with standard treatment is needed. Hopefully, this small study can encourage such studies.

Electrochemotherapy using intratumoral bleomycin for the treatment of basal cell carcinoma–Single Surgeon Results 2011–2015

Introduction: Electrochemotherapy (ECT) is a method by which the permeability of tumour cell membranes is increased through electroporation. With a permeable cell membrane previously administered Bleomycin is then able to diffuse in to tumour cells more easily, increasing efficacy of the drug.

Electrochemotherapy Using Intratumoral Bleomycin for the Treatment of Basal Cell Carcinoma–Single Surgeon Results 2011 - 2016

Electrochemotherapy Using Intratumoral Bleomycin for the Treatment of Basal Cell Carcinoma–Single Surgeon Results 2011 - 2016

Electrochemotherapy using intratumoral bleomycin for the treatment of basal cell carcinoma – Single surgeon results 2011–2015

Electrochemotherapy using intratumoral bleomycin for the treatment of basal cell carcinoma – Single surgeon results 2011–2015

Bleomycin electrochemotherapy in elderly metastatic breast cancer patients: clinical outcome and management considerations.

To evaluate the efficacy and toxicity of electrochemotherapy (ECT) in elderly metastatic breast cancer (BC) patients. Retrospective analysis of 55 patients with superficial metastases who underwent ECT according to the European Standard Operative Procedures of electrochemotherapy. Treatment schedule consisted of intravenous or intratumoral bleomycin followed by locally delivered electric pulses. Statistical comparisons were performed between two groups: the patients aged <70years (n=27) and those ≥70years (n=28). Treatment outcomes were as follows: complete response (CR) rate, local progression-free survival (LPFS), new lesions-free survival (NLFS), toxicity and patient compliance. Patient groups were comparable for clinical-pathological features, except for the number of comorbidities (P<.001). The median follow-up was 32months (range 6-53). Overall, CR rate was 40% and was significantly higher in elderly patients (57 vs. 26%, P=.023) and in patients with better performance status (PS=0-1, 53 vs. PS=2, 21%, P=.048), although local tumor control showed a trend for lower values (2-year LPFS, 67 vs. 93% among elderly and young patients, respectively; P=.061). Older women seemed less likely to progress outside the ECT field (2-year NLFS, 39 vs. 30%, P=.075), but discontinued treatment more frequently due to impaired performance status (P=.002). Local pain was graded ≥3, according to a 10-point visual analog scale, by 16/28 (57.1%) and 8/28 (28.6%) elderly patients at 4 and 8weeks, respectively. Wound debridement was required in 5/28 (18%) older women, due to G3 skin ulceration. Elderly BC patients are highly responsive to ECT and achieve durable local tumor control. Physicians should be aware of possible debilitating side effects, such as pain and skin toxicity. Performance status and frailty screening could be a helpful addition to improve patient selection.

Radiological findings following postsurgical intratumoral bleomycin injection for cystic craniopharyngioma

Objectives The purpose of this study was to compare the radiological findings before and after intratumoral bleomycin injection in patients with cystic craniopharyngioma so as to define the role of adjuvant intracavitary bleomycin chemotherapy for cystic craniopharyngiomas. Patients and methods Eleven patients whose craniopharyngioma was confirmed cytologically and/or histologically were retrospectively reviewed. The follow-up duration ranged from 9 to 79 months (mean, 31.6 months). Only the solid portion of the cystic craniopharyngiomas was excised before repeated injections of bleomycin (15–180 mg in total) into the cystic portion through an Ommaya reservoir were given. The patients were evaluated neuroradiologically before and after bleomycin administration. Results After the completion of all treatment cycles, the disappearance or shrinkage of the tumor was initially noted in all cases on follow-up CT and/or MR imaging studies. However, tumor recurrence was seen in four cases with a mixed tumor type. Conclusion Postoperative bleomycin injection in cystic craniopharyngioma does not appear to totally eradicate the tumor and does not stop tumor recurrence unless the cyst is the only portion of the craniopharyngioma that is left. Nevertheless, postoperative bleomycin injection decreases and stabilizes tumor size, and thus may be considered as an option of treatment modalities in patients with predominantly cystic craniopharyngiomas.

Intratumoral Therapy with Bleomycin for Cystic Craniopharyngiomas in Children

Surgical removal of cystic craniopharyngiomas in children is associated with significant operative morbidity and recurrence rates. The purpose of this study was to review our experience with a less invasive therapy, namely, intratumoral bleomycin, in the treatment of predominantly cystic craniopharyngiomas. All children with craniopharyngiomas treated at a tertiary care pediatric neurosurgical center since 1994, when bleomycin was first used, were reviewed retrospectively. Seven patients received intratumoral bleomycin therapy. Patients received 2–5 mg bleomycin per dose, 3 times per week, for 3–5 weeks as an initial course. Mean follow-up of these patients was 3 years. In 4 patients, treatment resulted in a significant decrease (>50%) in tumor size, which has remained stable. Two patients’ tumors progressed and underwent resection, and 1 patient had surgical removal because of persistent headaches, although no growth of residual tumor had been noted. One patient developed peritumoral edema as a result of bleomycin therapy. Intratumoral bleomycin is a useful alternative therapy for cystic craniopharyngiomas, and may control tumor growth and delay potentially harmful resection and/or radiotherapy in young children.

Post-traumatic temporal lobe lesions: natural history and treatment

CRANIOPHARYNGIOMAS: INTRATUMORAL CHEMOTHERAPY WITH BLEOMYCIN INCHILDREN AND ADOLESCENTS (ABSTRACT)*. THESIS. SAO PAULO, 1997. In 1985, Takahashi et al. published the promising results of seven patients with craniopharyngiomatreated with intratumoral bleomycin. Since then, two series (Broggi et al., 1989; Mottolese et al., 1996) ofpatients receiving the same type of treatment, with 18 patients each series, appeared in the literature. Inthis study we are presenting 21 patients, 10 males and 11 females, with predominantly cysticcraniopharyngioma, submitted to this intratumoral modality of treatment. Their age span from 3 to 19years old.Eleven cases were treated in neurosurgical departments in France and ten patients were treated inBrazil. The tumoral lesions were primary in 19 cases and recurrences in two cases. The length of timebetween the beginning of the symptoms and the diagnosis varied from one month to three years. Theassociation of endocrine and visual symptoms and symptoms related to intracranial hypertension were themost common clinical presentations. Endocrinopathies as isolated symptoms were present in seven patients.The technique for insertion of the catheter in the tumor cyst was microsurgical through a craniotomyin nine cases, stereotactically in nine cases and through a burr hole in three cases. The dose of bleomycinused varied from 2 to 10 mg per injection. The injections of the drug were done daily or in alternated days.The average total doses of bleomycin was 60 mg for each cycle. Seventeen patients received only onecycle of bleomycin, while three patients received two cycles and one patient received three cycles. Thelength of the follow-up varied from three months to six years.The results were classified as good in 13/21 cases. Among them the tumor completely disappearedin three, and in nine patients occurred a reduction in size of more than 50%.The technique used in this series did not add any endocrinological morbidity. Two complicationswere detected: a transient optic neuritis during the second cycle of treatment and a seizure probablyrelated to extratumoral leakage of the drug. Only three patients presenting with hydrocephalus demandedsurgical diversion of cerebrospinal fluid before the intratumoral treatment with bleomycin.Six patients from the series were submitted to craniotomy for direct approach of the tumor aftertreatment with bleomycin. Three because of the cystic recurrence: two because of the complicationspreviously mentioned and one to approach the solid part of the tumor. One patient received radiotherapictreatment for control of the solid part of the craniopharyngioma after treatment with bleomycin.KEY WORDS: craniopharyngioma, intratumoral chemotherapy, bleomycin.*Craniofaringiomas: quimioterapia intratumoral com bleomicina em criancas e adolescentes. Tese de Mestrado, EscolaPaulista de Medicina – Universidade Federal de Sao Paulo, UNIFESP (Area: Neurocirurgia). Orientador:Sergio Cavalheiro.**Address: Rua Apeninos 471 / 115, 01533-000 Sao Paulo SP, Brasil.POST-TRAUMATIC TEMPORAL LOBE LESIONS: NATURAL HISTORY AND TREATMENT(ABSTRACT)*. THESIS. SAO PAULO, 1997. This is a prospective study of 69 patients with traumatic temporal lobe lesions (TTLL). Computerizedtomography (CT) scans were performed in the first 36 hours, 7 and 30 days after the trauma. Lesions were

Treatment of hepatic metastases of colorectal cancer by electrochemotherapy: An experimental study in the rat

Background: Electrochemotherapy, which consists of local or systemic administration of a cytotoxic agent followed by application of electric pulses to a tumor, has proved effective for various types of tumors in animals and for cutaneous and head and neck cancers in human beings. This is the first study to investigate the efficacy of electrochemotherapy for treatment of hepatic metastases of colorectal cancer in the rat. Methods: After induction of a solitary hepatic metastasis in 36 male BDIX rats, the animals were randomized to one of four groups: B–E– (no treatment), B+E-– (intratumoral bleomycin), B–E+ (application of electric pulses to the tumor), and B+E+ (electrochemotherapy: intratumoral bleomycin followed by application of electric pulses). Results: Groups B–E– and B–E+ had no tumor response. Group B+E- had one partial response. Group B+E+ had seven partial responses and two complete responses. The difference in terms of response between group B+E+ and the other three groups was statistically significant ( P < .05). Comparison of the mean posttherapy tumor volumes (B–E–, 50.6 mm 3; B+E–, 58.7 mm 3; B–E+, 46 mm 3; and B+E+, 5.65 mm 3) revealed a significantly smaller residual tumor in group B+E+ than in the other three groups ( P < .05). Conclusions: Electrochemotherapy is an effective means to reduce the volume of hepatic metastases of colorectal cancer in the rat. Additional research is required to determine the optimum treatment duration, dose effects, volume of tumor that can be treated by electrochemotherapy, and impact on survival. Such experimental studies are indispensable prerequisites for clinical trials. (Surgery 1998;124:536-40.)

Preoperative chemotherapy in head and neck cancer

We submit our present work dealing with stage III and IV epidermoid head and neck carcinomas which have been referred for preoperative chemotherapy. Our selection of one of the two following combinations is based on the histological differentiation of the tumour and general state of the patient. Intravenous Bleomycin plus intratumoral oil Bleomycin, or Continuous infusion of Cisplatin and 5 Fluoro-uracil for six days. We present the results obtained in 37 patients, and the complications which arose.