bacteriochlorophylls and Prostatic-Neoplasms

The increase of the diagnosis of low risk prostate cancer translates into a new clinical entity, for which active surveillance may not be always enough and conventional therapies are clearly overtreatment. Faced with the necessity of giving a therapeutic answer to these patients, and facilitated by the technological advances in the imaging field and new energy sources, the interest is centered in the clinical development of focal therapies as an alternative with minimal morbidity and oncologically safe. As a part of the review carried out in this monographic issue, this article focus on the features relative to the preclinical and clinical development of laser ablative therapy and the innovative photodynamic vascular therapy with soluble TOOKAD®. With this aim we performed an exhaustive bibliographic search, updated to February 2016, in the greater databases, including original articles and reviews in reference to the object of this review, without restrictions for year of publication. This article reviews the preclinical and clinical development of these innovative ablative techniques in the field of focal therapy for low risk prostate cancer.

Topics: Bacteriochlorophylls; Blood Vessels; Combined Modality Therapy; Humans; Laser Therapy; Male; Photochemotherapy; Prostatectomy; Prostatic Neoplasms; Risk

To evaluate the 6-month effects of the recommended drug and light dosage in focal vascular-targeted photodynamic therapy (VTP) using TOOKAD(®) Soluble in patients with localized prostate cancer (LPCa).. We performed a pooled analysis of 117 men with LPCa, PSA <10 ng/mL, and Gleason score ≤ 7 (3 + 4), from 3 studies who received a 10-min intravenous infusion of a single dose of 4 mg/kg TOOKAD(®) Soluble, activated by a 753-nm light at 200 J/cm delivered in the prostate by transperineal fibres under transrectal ultrasound guidance. Primary endpoint was 6-month negative biopsies in the treated lobe(s). PSA was measured at month 1, 3, and 6. Magnetic resonance imaging was performed at day 7, month 3, and 6. International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and adverse events were reported at day 7, month 1, 3, and 6.. Month 6 negative biopsy rate was 68.4 % in the overall evaluable population (N = 114) and 80.6 % for patients treated by hemiablation with light density index (LDI) ≥ 1 (N = 67). Mean prostate necroses at week-1 were 76.5 and 86.3 %, respectively. In both groups, PSA levels at month 6 decreased by 2.0 ng/mL. Small changes from baseline for IPSS and IIEF-5 indicated a slight improvement in urinary function and a slight deterioration in sexual function.. Focal VTP treatment with TOOKAD(®) Soluble at 4 mg/kg and 200 J/cm resulted in a negative 6-month biopsy rate of 68.4 % for the whole population and 80.6 % for patients treated by hemiablation with LDI ≥ 1. The treatment was well tolerated. Two phase III studies will reach completion in early 2015.

Topics: Bacteriochlorophylls; Clinical Trials, Phase II as Topic; Humans; Male; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms; Treatment Outcome

Photodynamic therapy (PDT) is well known for its direct cytotoxicity of the free radical-producing photochemical reaction, indirect mechanisms of action including modulation of intrinsic anti-tumour immune activity, and occlusion of pathologically altered tumour vessels leading to tumour ischaemia. The aim of this work is to critically review the evidence base for the use of vascular targeted PDT (VTP) to treat low-risk prostate cancer, and to discuss perspectives and challenges yet to be overcome. A brief general overview of focal prostate cancer therapy was provided, followed by a discussion of both basic and clinical research pertaining to prostate cancer VTP, with a focus on the palladium-based WST-09 and WST-11 photosensitisers.. Literature on VTP for prostate cancer with the fallowing medical subject headings search terms: prostate cancer, photodynamic therapy, vascular targeted photodynamic therapy, bacteriopheophorbide were reviewed. The articles were selected by their relevance to the topic.. The clinical and basic research data available to date show much promise for WST-09, and WST-11 based VTP eventually joining the standard urologist's armamentarium against prostate cancer. With good reported tolerability and efficacy VTP can be proposed as an intermediate treatment for local low risk disease, halfway between watchful waiting and radical therapy.

Topics: Animals; Bacteriochlorophylls; Humans; Male; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms; Risk Assessment

Debate is ongoing about the treatment of organ-confined prostate cancer, particularly in men who have low-risk disease detected by PSA screening. A balance is needed between the harms and benefits of treatment. New techniques are being developed that aim to offer similar treatment effects to current radical therapies, while reducing the associated harmful effects of these treatments. In this Review, we explore the potential of one such technique, photodynamic therapy (PDT), for the treatment of organ-confined prostate cancer. PDT uses a photosensitizing drug that is activated in the prostate by low-power laser light, delivered using optical fibers. The fibers are placed within needles in the prostate, guided by transrectal ultrasound and a perineal template. Following the activation of the photosensitizer by light, and the formation of reactive oxygen species, necrosis occurs at the site of interaction between the photosensitizer, light and oxygen. Clinical studies are underway to investigate the use of PDT for primary and salvage treatment of organ-confined prostate cancer. We review these studies, the potential strategies for enhanced photodynamic effects, and the current limitations of PDT for prostate cancer.

Topics: Bacteriochlorophylls; Forecasting; Humans; Male; Mesoporphyrins; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms

To assess the medium-term tumor control in patients with localized prostate cancer (PCa) treated with vascular-targeted photodynamic (VTP) therapy with TOOKAD Soluble WST11 (VTP) and to assess the medium-term tolerability of the treatment.. During the clinical phase II studies, 68 patients were treated with VTP under optimal treatment conditions (WST11 at 4mg/kg, light energy at 200J/cm, and a light density index ≥1) and have been included in a 3.5-yr follow-up.. Post-interventional visits were scheduled every 6 mo and conducted as per local standard practice in each study center. Cancer-free status was assessed by means of prostate-specific antigen kinetics, multiparametric magnetic resonance imaging and/or prostate biopsies.. At the end of the 3.5-yr follow-up, overall successful focal ablation was achieved for 51 patients (75%). Cancer was identified in the untreated lobe in 17 patients (25%). In total, 34 patients (50%) were cancer-free in both the prostate lobes. In case of recurrent/persistent malignancy, the Gleason score remained consistent or changed at the maximum by one point (upgrading by 1 Gleason point to 3+4 for eight patients and 4+3 for two patients). There were 64 related adverse events (AEs): 48% were Clavien grade I, 47% were grade II, and 5% were grade III. There were no Clavien grade IV and V AEs. Limitations included small sample size and heterogeneity in the follow-up for some centers.. VTP is a safe and efficient treatment and represents an alternative option for localized low-risk PCa management over the medium term. Precise diagnostic methods and imaging tools are thereby essential requirements to ensure safe and complete targeted therapy.. In this report, we looked at the medium-term outcomes of focal photodynamic therapy for early-stage prostate cancer. We found that this form of treatment is efficient and might have the potential to become a therapeutic option for low-risk cancer. Effectiveness depends on precise diagnostic methods, such as magnetic resonance imaging and accurate biopsy.

Topics: Aged; Bacteriochlorophylls; Biopsy; Combined Modality Therapy; Follow-Up Studies; Humans; Male; Middle Aged; Molecular Targeted Therapy; Multiparametric Magnetic Resonance Imaging; Neoplasm Grading; Photochemotherapy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment; Treatment Outcome

We assessed the midterm oncologic outcomes of vascular targeted photodynamic therapy with padeliporfin for low risk prostate cancer treatment.. We prospectively assessed all patients treated with vascular targeted photodynamic therapy for low risk prostate cancer at our center. Patients were followed every 6 months. All patients underwent prostate biopsies 6 months after treatment or when there was biological or clinical progression. The primary end point was progression-free survival. Secondary end points were absent clinically significant cancer in the treated lobes, radical therapy and the prostate specific antigen rate. Variables were compared with the chi-square, Mann-Whitney or Wilcoxon test. Progression-free survival is reported with Kaplan-Meier curves.. A total of 82 men were treated with vascular targeted photodynamic therapy. Median followup was 68 months (range 6 to 89). Median progression-free survival was 86 months (95% CI 82-90). Median prostate specific antigen decreased significantly by 41% 6 months after treatment and it remained stable during followup (p <0.001). A total of 115 lobes were treated and absent clinically significant cancer was achieved in 94 (82%). Of the 82 patients 20 (24%) underwent radical therapy, including radical prostatectomy in 18 and brachytherapy in 2, at a median of 22 months (range 6 to 86). Study limitations include a single arm design, small population size and midterm followup.. Padeliporfin vascular targeted photodynamic therapy for low risk prostate cancer achieved an 82% rate of absent clinically significant cancer in treated lobes and 76% of patients avoided radical therapy at a median followup of 68 months. However, longer followup is required to determine long-term outcomes.

Topics: Aged; Bacteriochlorophylls; Follow-Up Studies; Humans; Male; Middle Aged; Photochemotherapy; Progression-Free Survival; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Treatment Outcome

Vascular targeted photodynamic therapy (VTP) with WST11 is a novel non-thermal focal treatment for localized prostate cancer that has shown favorable and early efficacy results in previously published studies. In this work, we investigate the efficiency of automatic dosimetric treatment planning. An action model established in a previous study was used in an image-guided optimization scheme to define the personalized optimal light dose for each patient. The calculated light dose is expressed as the number of optical cylindrical fibers to be used, their positions according to an external insertion grid, and the lengths of their diffuser parts. Evaluation of the method was carried out on data collected from 17 patients enrolled in two multi-centric clinical trials. The protocol consisted of comparing the method-simulated necrosis to the result observed on day 7 MR enhanced images. The method performances showed that the final result can be estimated with an accuracy of 10%, corresponding to a margin of 3 mm. In addition, this process was compatible with clinical conditions in terms of calculation times. The overall process took less than 10 min. Different aspects of the VTP procedure were already defined and optimized. Personalized treatment planning definition remained as an issue needing further investigation. The method proposed herein completes the standardization of VTP and opens new pathways for the clinical development of the technique.

Topics: Bacteriochlorophylls; Dose-Response Relationship, Radiation; Humans; Male; Necrosis; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms; Radiotherapy Planning, Computer-Assisted

Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial.. This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894.. Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients).. Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy.. Steba Biotech.

Topics: Adult; Aged; Aged, 80 and over; Bacteriochlorophylls; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Photochemotherapy; Photosensitizing Agents; Population Surveillance; Prognosis; Prostatic Neoplasms; Risk Assessment; Survival Rate

Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is a form of tissue ablation that may be used therapeutically for localized prostate cancer. To study dosing parameters and associated treatment effects we performed a prospective, multicenter, phase I/II trial of WST11 vascular targeted photodynamic therapy of prostate cancer.. A total of 30 men with unilateral, low volume, Gleason 3 + 3 prostate cancer were enrolled at 5 centers after local institutional review board approval. Light energy, fiber number and WST11 dose were escalated to identify optimal dosing parameters for vascular targeted photodynamic therapy hemi-ablation. Men were treated with photodynamic therapy and evaluated by posttreatment magnetic resonance imaging and biopsy. Prostate specific antigen, light dose index (defined as fiber length/desired treatment volume), toxicity and quality of life parameters were recorded.. After dose escalation 21 men received optimized dosing of 4 mg/kg WST11 at 200 J energy. On posttreatment biopsy residual prostate cancer was found in the treated lobe in 10 men, the untreated lobe in 4 and both lobes in 1. At a light dose index of 1 or greater with optimal dosing in 15 men 73.3% had a negative biopsy in the treated lobe. Six men undergoing retreatment with the optimal dose and a light dose index of 1 or greater had a negative posttreatment biopsy. Minimal effects were observed on urinary and sexual function, and overall quality of life.. Hemi-ablation of the prostate with WST11 vascular targeted photodynamic therapy was well tolerated and resulted in a negative biopsy in the treated lobe in the majority of men. Dosing parameters and the light dose index appear related to tissue response as determined by magnetic resonance imaging and biopsy. These parameters may serve as the basis for further prospective studies.

Topics: Ablation Techniques; Aged; Bacteriochlorophylls; Biopsy; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Grading; Photochemotherapy; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Treatment Outcome; United States

To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer.. In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months.. In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP.. Treatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%).

Topics: Aged; Antineoplastic Agents; Bacteriochlorophylls; Biopsy; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms; Radiation Dosage

Low-risk prostate adenocarcinoma is classically managed either with active surveillance or radical therapy (such as external radiotherapy or radical prostatectomy), but both have significant side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy proposed as an alternative approach for localized, low-volume, and low-Gleason score (≤6) carcinomas. We report histological modifications observed in prostate biopsies of 56 patients, performed 6 months after VTP using the photosensitizer TOOKAD® Soluble (WST11) and low-energy laser administered in the tumor area transperineally by optic fibers. In 53 patients, we observed sharply demarcated hyaline fibrotic scars, with or without rare atrophic glands, sometimes reduced to corpora amylacea surrounded by giant multinuclear macrophages. Mild chronic inflammation, hemosiderin, and coagulative necrosis were also observed. When residual cancer was present in a treated lobe (17 patients), it was always located outside the scar, most often close to the prostate capsule, and it showed no therapy-related modification. Histopathological interpretation of post-WST11 VTP prostate biopsies was straightforward, in contrast with that of prostate biopsies after radio or hormonal therapy, which introduces lesions difficult to interpret. VTP resulted in complete ablation of cancer in the targeted area.

Topics: Adenocarcinoma; Aged; Bacteriochlorophylls; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms

To evaluate the optimal treatment conditions and effects of TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD(®) Soluble VTP treatment in patients with localised prostate cancer.. Men (aged >18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size <60 mL would receive 4 mg/kg TOOKAD(®) Soluble and patients with prostate size ≥60 mL would receive 6 mg/kg TOOKAD(®) Soluble both activated with 200 J/cm light). In part two, patients were assigned to one of two treatment groups based on predefined criteria and received either 4 or 6 mg/kg TOOKAD(®) Soluble and 200 or 300 J/cm light. VTP was conducted under general anaesthesia using TOOKAD(®) Soluble administered intravenously and activated by light-diffusing fibres within the prostate via the perineum. Follow-up was conducted for 6 months. Magnetic resonance imaging (MRI) carried out at 1 week after VTP and transrectal prostate biopsy at 6 months were the key endpoints. Adverse event (AE) recording and patient-reported outcome measures were collected.. In all, 86 patients were enrolled in the study and 85 patients received treatment. Of the 85 treated patients, one patient discontinued (due to withdrawal of consent). At 6 months, 61/83 (74%) patients who underwent prostate biopsy had histopathology that was negative for prostate cancer (95% confidence interval (CI) 62.7-82.6%). Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), which are considered optimal treatment parameters, 38/46 (83%) patients had histopathology from the biopsies that was negative for prostate cancer at 6 months (95% CI 68.6-92.2%; P < 0.001). The mean percentage of necrosis of the targeted prostate tissue at 7 days after VTP was 78% overall (83 patients) with extraprostatic necrosis reported in 76% (63/83) of patients. Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), the mean 7-day necrosis percentage was 88% (46 patients) with extraprostatic necrosis reported in 72% (33/46) of patients. All occurrences of extraprostatic necrosis were considered clinically acceptable and none were associated with any clinical sequelae. The mean percentage prostate necrosis at 7 days was statistically significantly higher (P < 0.001) in patients treated with a therapeutic light density index (LDI) of ≥1 than those treated with a LDI of <1. The percentage of patients with negative biopsies at 6 months was also higher in patients treated with a therapeutic LDI of ≥1 than those treated with a LDI of <1 (78.6% and 63.0%, respectively). In all, 87% (75/86) of patients reported at least one treatment-emergent AE during the study. Most AEs were mild or moderate in intensity and considered related to the technical procedures of the study. No treated patients had hypotension or discontinued due to AEs. Eight patients (9.3%) had serious AEs; none resulted in discontinuation from the study.. Biopsy data, post-treatment dynamic contrast-enhancement MRI at 1 week after VTP and analysis of the safety data have shown that 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light are the optimal treatment conditions for the VTP procedure resulting in >80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer.

Topics: Aged; Bacteriochlorophylls; Biopsy; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Injections, Intravenous; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Photochemotherapy; Prostate; Prostatic Neoplasms; Quality of Life; Retrospective Studies; Treatment Outcome

To report on the efficacy of TOOKAD (WST 09; NegmaLerads, Magny-Les-Hameaux, France) vascular-targeted photodynamic therapy (VTP) as a method of whole-prostate ablation in patients with recurrent localized prostate cancer after the failure of external beam radiotherapy (EBRT).. Patients received a fixed photosensitizer dose of 2 mg/kg and patient-specific light doses as determined by computer-aided treatment planning. Up to six cylindrical light-diffusing delivery fibres were placed transperineally in the prostate under ultrasonographic guidance. The treatment response was assessed by measuring serum prostate-specific antigen (PSA) levels, lesion formation (avascular areas of tissue) measured on 7-day gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) and a 6-month biopsy.. Treatment of the whole prostate was possible with minimal effects on surrounding organs. An increased light dose improved the tissue response, with MRI-detectable avascular lesions, encompassing up to 80% of the prostate in some patients. A complete response, as determined by the 6-month biopsy, required that patients received light doses of at least 23 J/cm(2) in 90% of the prostate volume (D(90) > 23 J/cm(2)). Of the 13 patients who received at least this light dose, eight were biopsy-negative at 6 months. In this group of eight patients, PSA levels decreased and did so to negligible levels for those patients with a baseline PSA level of <5 ng/mL. Side-effects were modest and self-limited in most patients; there were recto-urethral fistulae in two patients, one of which closed spontaneously.. TOOKAD-VTP can produce large avascular regions in the irradiated prostate, and result in a complete negative-biopsy response at high light doses. A response rate of more than half for those patients receiving the highest light doses shows the clinical potential of TOOKAD-VTP to manage recurrence of prostatic carcinoma after EBRT.

Topics: Bacteriochlorophylls; Biopsy; Dose-Response Relationship, Drug; Humans; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Photochemotherapy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

Tookad is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external beam radiation therapy.. Patients received escalating drug doses of 0.1 to 2 mg/kg at a fixed light dose of 100 J/cm or escalated light doses of 230 and 360 J/cm at the 2 mg/kg dose. Four optical fibers were placed transperineally in the prostate, including 2 for light delivery and 2 for light dosimetry. Treatment response was assessed primarily by hypovascular lesion formation on contrast enhanced magnetic resonance imaging and transrectal ultrasound guided biopsies targeting areas of lesion formation and secondarily by serum prostate specific antigen changes.. Tookad vascular targeted photodynamic therapy was technically feasible. The plasma drug concentration was negligible by 2 hours after infusion. In the drug escalation arm 3 of 6 patients responded, as seen on magnetic resonance imaging, including 1 at 1 mg/kg and 2 at 2 mg/kg. The light dose escalation demonstrated an increasing volume of effect with 2 of 3 patients in the first light escalation cohort responding and all 6 responding at the highest light dose with lesions encompassing up to 70% of the peripheral zone. There were no serious adverse events, and continence and potency were maintained.. Tookad vascular targeted photodynamic therapy salvage therapy is safe and well tolerated. Lesion formation is strongly drug and light dose dependent. Early histological and magnetic resonance imaging responses highlight the clinical potential of Tookad vascular targeted photodynamic therapy to manage post-external beam radiation therapy recurrence.

Topics: Bacteriochlorophylls; Biopsy; Brachytherapy; Dose-Response Relationship, Drug; Humans; Infusions, Intravenous; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Photochemotherapy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

The aim of the study was to assess quality of life (QoL), decision involvement, and decisional regret after treatment with vascular-targeted photodynamic therapy (VTP) (TOOKAD®) for unilateral low-risk prostate cancer.. Validated questionnaires (EORTC QLQ-C30 and QLQ-PR25) capturing QoL post-treatment, involvement in decision-making (Control Preferences Scale) and decision regret (Decisional Regret Scale), were given to patients at the 12-month visit after undergoing VTP at our institution between May 2018 and February 2021.. Out of 44 patients, 36 patients were included in this study and 31 (86.1%) responded to the questionnaires. Mean overall health score capturing QoL at 12 months was 79.3 (standard deviation: ±18.1). 70.9% of the patients (n = 22) had no decision regret, and 67.8% of men (n = 21) had an active role in decision-making. In control biopsy at 12 months post-treatment, 19.4% of patients (n = 7) presented with local recurrence and progression to higher Gleason score (GS) was found in 13.8% of patients (n = 5). Patients (n = 3) presenting with tumor recurrence or progression to higher GS in control biopsy showed a significantly higher level of decision regret (p < 0.009).. Only 9.7% of men (n = 3) felt a strong emotion of regret at 12 months after VTP. Level of decision regret was significantly higher in patients with local recurrence or tumor progression detected in control biopsy. QoL was stable after VTP.

Topics: Bacteriochlorophylls; Decision Making; Emotions; Humans; Male; Photochemotherapy; Prostatic Neoplasms; Quality of Life

Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes.. We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes.. Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment.. Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons.

Topics: Aged; Bacteriochlorophylls; Feasibility Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Postoperative Complications; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Salvage Therapy; Treatment Outcome

To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP).. Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study.. In the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported.. Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa.

Topics: Adult; Aged; Aged, 80 and over; Bacteriochlorophylls; Humans; Latin America; Male; Middle Aged; Photochemotherapy; Prostatic Neoplasms; Quality of Life

Topics: Bacteriochlorophylls; Biopsy; Disease Progression; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Photochemotherapy; Photosensitizing Agents; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk; Time Factors; Treatment Outcome

To investigate feasibility, safety, and efficacy of salvage radical prostatectomy (RP) for recurrent prostate cancer (PCa) after focal treatment with TOOKAD(®) Soluble vascular-targeted photodynamic therapy (VTP).. Nineteen patients underwent RP after biopsy-proven PCa post-focal VTP. We reported: operation time, blood loss, transfusion, complications, urethral catheterization time, functional outcomes, and short-term oncologic outcomes.. Median age was 64 years (58-70). Median PSA before VTP was 6.30 ng/ml (3.20-9.80). Median delay between VTP and RP was 17 months (8-48). Median blood loss was 400 ml (100-1,000). Median operation time was 150 min (90-210), median urethral catheterization time was 7 days (5-18), and median hospital stay was 7 days (4-21). There was no perioperative mortality. Three patients had related per-operative complications: one pelvic hematoma (150 cc) (Clavien IIIa), one per-operative transfusion (900 cc hemorrhage) (Clavien II), and one superficial wound infection (Clavien I). After a median follow-up of 10 months (1-46), 13 were completely continent (68 %), five needed ≤1 pad/day, and one needed 3 pads/day (Clavien I). Severe erectile dysfunction was observed before and after RP (respectively 8 and 18). Ten patients regained potency with appropriate treatment. Median postoperative PSA was 0.02 ng/ml (<0.01-0.38) and remained undetectable for 16 patients (84 %). Nine patients had positive margins and six underwent complementary radiotherapy. Positive margins were significantly associated with bilateral VTP [risk ratio = 4.3, 95 % confidence interval (1.6-11.7), p = 0.003].. Salvage RP after VTP treatment was feasible, safe, and efficient to treat most of the locally recurrent PCa. Short-term oncologic and functional outcomes were promising, but further studies are required.

Topics: Aged; Bacteriochlorophylls; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Prostatectomy; Prostatic Neoplasms; Salvage Therapy; Treatment Outcome

Vascular-targeted photodynamic therapy with TOOKAD(®) Soluble is an innovative focal therapy procedure assessed in localized prostate cancer treatment.. This mini-invasive technique destroys targeted tissues using a photosensitizer [TOOKAD(®) Soluble (WST11), STEBA Biotech] activated by laser light in the presence of oxygen. Its application for prostate cancer requires intravenous infusion of TOOKAD(®) Soluble and the illumination of the targeted area by transperineal optical fibers inserted under trans-rectal ultrasound guidance under general anesthesia.. Based on the experience gained through hundreds of procedures, we describe here the standardized technique of vascular-targeted photodynamic therapy with TOOKAD(®) Soluble defined during the phase II and III trials.

Topics: Bacteriochlorophylls; Humans; Male; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms

Topics: Bacteriochlorophylls; Humans; Male; Photochemotherapy; Prostatic Neoplasms

Topics: Bacteriochlorophylls; Humans; Male; Photochemotherapy; Prostatic Neoplasms

Focal therapies are new options for the treatment of localized prostate cancer. Vascular-targeted photodynamic therapy (VTP) with WST11 is one of these options. The aim of this treatment is to destroy a targeted area of the prostate by the associated action of the WST11 drug, light exposure and oxygen. The procedure is performed under general anesthesia. Fibers are introduced trans-perineally in the prostate by ultrasound guidance. The injection of WST11 is then performed with light illumination of the specific targeted area. Current data report 83% negative biopsies 6 months after treatment with good tolerance of the treatment. However, VTP still needs to be evaluated.

Topics: Bacteriochlorophylls; Humans; Male; Photochemotherapy; Prostatic Neoplasms

This study describes a multimodality images based platform to drive photodynamic therapies of prostate cancer using WST 11 TOOKAD Soluble drug. The platform integrates a pre-treatment planning tool based on magnetic resonance imaging and a per-treatment guidance tool based on transrectal ultrasound images. Evaluation of the platform on clinical data showed that prediction of the therapy outcome was possible with an accuracy of 90 %.

Topics: Bacteriochlorophylls; Calibration; Equipment Design; Gadolinium; Humans; Image Processing, Computer-Assisted; Imagery, Psychotherapy; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Photochemotherapy; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Reproducibility of Results; Treatment Outcome; Ultrasonography

Interstitial photodynamic therapy is becoming an interesting modality to treat some early stage prostate cancers. A light-sensitive drug is injected to the patient and activated by light using optical fibres inserted inside the prostate. In this work, we were interested in the characterization of the light action model for the WST11 (Tookad® Soluble) drug. A retrospective analysis was performed on results from 28 patients enrolled in phase I and II trials with the WST11 drug. A drug dose of 4 mg/kg patient, dose light of 200 J cm(-1) and wavelength of 753 nm were used. Correlation between the illuminated volume and the obtained necrosis, measured at day 7 MR images, was clearly established. This result suggests that photodynamic therapy planning is possible based on this model.

Topics: Bacteriochlorophylls; Humans; Male; Models, Biological; Photochemotherapy; Prostate; Prostatic Neoplasms; Retrospective Studies; Solubility; Time Factors; Treatment Outcome

Epidemiologic and pathologic features of prostate cancer have given rise to an interest in focal treatment for carefully selected patients. Prostate cancer remains highly prevalent, particularly in the United States and Europe. As screening programs have become more aggressive and widespread, a substantial proportion of men diagnosed with localized prostate cancer have disease characteristics associated with a low risk of progression. Treatments such as radical prostatectomy and radiation therapy can lead to durable recurrence-free survival in most patients but carry variable risks of bowel, urinary, and sexual side effects. Few men and few urologists are comfortable leaving a potentially curable prostate cancer untreated. Focal therapy offers an attractive alternative to the patient faced with a choice between aggressive local intervention (radiation or surgery) and watchful waiting. Contemporary diagnostic biopsy strategies and imaging tools and the development of predictive statistical models (nomograms) have led to improvements in tumor characterization and risk-stratification, making focal therapy a viable treatment option for specific men. This article reviews the rationale and indications for focal therapy and highlights vascular-targeted photodynamic therapy (PDT) as one of many promising focal therapy techniques.

Topics: Animals; Bacteriochlorophylls; Humans; Magnetic Resonance Imaging; Male; Photochemotherapy; Prostatic Neoplasms

To prospectively evaluate the magnetic resonance (MR) imaging appearance of the prostate and periprostatic tissues after vascular targeted photodynamic therapy (VTP) with palladium-bacteriopheophorbide for locally recurrent carcinoma after external beam radiation therapy.. Informed consent was obtained from all patients, and approval was obtained from the ethics review boards of all participating institutions. Nonenhanced T2-weighted and dynamic gadolinium-enhanced T1-weighted MR imaging examinations were performed at baseline and 1 week, 4 weeks, and 6 months after VTP in 25 men (age range, 58-83 years; mean age, 73 years) as part of a prospective phase I/II trial. Percentage of MR-depicted necrosis was defined as the volume of nonenhancing prostatic tissue 1 week after VTP divided by the volume of the prostate. Patterns of intra- and extraprostatic necrosis were recorded. Pearson correlation coefficients were used to test correlations between necrosis and prostate-specific antigen level.. Contrast material-enhanced T1-weighted MR images obtained 1 week after therapy showed necrosis in all patients. Treatment margins were irregular in 21 of 25 patients. T2-weighted images showed no clear treatment boundaries in any patient. Extraprostatic necrosis involved the puborectalis or levator ani muscles in 22, obturator internus muscle in 12, periprostatic veins in three, pubic bone marrow in four, and anterior rectal wall in nine of the 25 patients. The neurovascular bundle appeared to be spared in all patients. Percentage of MR-depicted intraprostatic necrosis was correlated with percentage decrease in prostate-specific antigen level (from baseline) at 4 weeks (r=0.41, P=.04) and 12 weeks (r=0.45, P=.02).. Contrast-enhanced MR imaging depicts irregular margins of intraprostatic treatment effect. This finding suggests varied tissue sensitivities to VTP with palladium-bacteriopheophorbide.

Topics: Aged; Aged, 80 and over; Bacteriochlorophylls; Contrast Media; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Photochemotherapy; Prospective Studies; Prostatic Neoplasms; Treatment Outcome

Photodynamic therapy (PDT) mediated with Tookad (Pd-bacteriopheophorbide, WST09) was investigated pre-clinically as part of a program to develop an alternative modality for treating prostate cancer.. Spontaneous canine prostate cancer and normal canine prostate were used as the animal models. Interstitial PDT was performed by IV infusion of the photosensitizer and irradiating the prostates with a diode laser (763 nm). The prostates were harvested 1-week post-PDT and subjected to histopathologic examinations. The effects of the drug doses and light doses were studied for one- and two-session PDT. Pharmacokinetics were studied using HPLC assay. The feasibility of using perfusing CT scans for assessing PDT lesions was also evaluated.. Tookad is a vascular-acting drug and clears rapidly from the circulation. Tookad-PDT-induced lesions, in both normal and cancerous prostates, were characterized by marked hemorrhagic necrosis.. Tookad-PDT is very effective in ablating prostatic tissue through its vascular effects.

Topics: Animals; Bacteriochlorophylls; Dogs; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Infusions, Intravenous; Male; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms

The aim of this study was to evaluate the effects of photodynamic therapy (PDT) using a novel palladium bacteriopherophorbide photosensitizer TOOKAD (WST09) on canine prostate that had been pretreated with ionizing radiation. To produce a physiological and anatomical environment in canine prostate similar to that in patients for whom radiotherapy has failed, canine prostates (n = 4) were exposed to ionizing radiation (54 Gy) 5 to 6 months prior to interstitial TOOKAD-mediated PDT. Light irradiation (763 nm, 50-200 J/cm at 150 mW/cm from a 1-cm cylindrical diffusing fiber) was delivered during intravenous infusion of TOOKAD at 2 mg/kg over 10 min. Interstitial measurements of tissue oxygen profile (pO(2)) and of local light fluence rate were also measured. The prostates were harvested for histological examination 1 week after PDT. The baseline pO(2) of preirradiated prostate was in the range 10-44 mmHg. The changes in relative light fluence rate during PDT ranged from 12 to 43%. The acute lesions were characterized by hemorrhagic necrosis, clearly distinguishable from the radiotherapy-induced pre-existing fibrosis. The lesion size was correlated with light fluence and comparable to that in unirradiated prostate treated with a similar TOOKAD-PDT protocol. There was no noticeable damage to the urethra, bladder or adjacent colon. The preliminary results obtained from a small number of animals indicate that TOOKAD-PDT can effectively ablate prostate pretreated with ionizing radiation, and so it may provide an alternative modality for those prostate cancer patients for whom radiotherapy has failed.

Topics: Animals; Bacteriochlorophylls; Combined Modality Therapy; Dogs; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Light; Male; Oxygen; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms; Radiation Dosage; Radiation, Ionizing

Small cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was therefore tempting to evaluate the response of this violent malignancy and its bone lesions to Pd-Bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive non-epithelial solid tumors. TOOKAD is a novel bacteriochlorophyll-derived, second-generation photosensitizer recently, developed by us for the treatment of bulky tumors. This photosensitizer is endowed with strong light absorbance (epsilon(0) approximately 10(5) mol(-1) cm(-1)) in the near infrared region (lambda=763nm), allowing deep tissue penetration. The TOOKAD-PDT protocol targets the tumor vasculature leading to inflammation, hypoxia, necrosis and tumor eradication. The sensitizer clears rapidly from the circulation within a few hours and does not accumulate in tissues, which is compatible with the treatment of localized tumor and isolated metastases. Briefly, male CD1-nude mice were grafted with the human SCCP (WISH-PC2) in 3 relevant anatomic locations: subcutaneous (representing tumor mass), intraosseous (representing bone metastases) and orthotopically within the murine prostate microenvironment. The PDT protocol consisted of i.v. administration of TOOKAD (4 mg/kg), followed by immediate illumination (650-800 nm) from a xenon light source or a diode laser emitting at 770 nm. Controls included untreated animals or animals treated with light or TOOKAD alone. Tumor volume, human plasma chromogranin A levels, animal well being and survival were used as end points. In addition, histopathology and immunohistochemistry were used to define the tumor response. Subcutaneous tumors exhibited complete healing within 28-40 days, reaching an overall long-term cure rate of 69%, followed for 90 days after PDT. Intratibial WISH-PC2 lesions responded with complete tumor elimination in 50% of the treated mice at 70-90 days after PDT as documented histologically. The response of the orthotopic model was also analyzed histologically with similar results. The study with this model suggests that TOOKAD-based PDT can reach large tumors and is a feasible, efficient and well-tolerated approach for minimally invasive treatment of local and disseminated SCCP.

Topics: Animals; Bacteriochlorophylls; Bone Diseases; Carcinoma, Small Cell; Chromogranin A; Chromogranins; Humans; Immunoenzyme Techniques; Magnetic Resonance Imaging; Male; Mice; Mice, Nude; Models, Animal; Neoplasm Transplantation; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms; Transplantation, Heterologous; Treatment Outcome; Tumor Cells, Cultured

Photodynamic therapy (PDT) uses light to activate a photosensitizer to achieve localized tumor control. In this study, PDT mediated by a second-generation photosensitizer, palladium-bacteriopheophorbide WST09 (Tookad) was investigated as an alternative therapy for prostate cancer. Normal canine prostate was used as the animal model. PDT was performed by irradiating the surgically exposed prostate superficially or interstitially at 763 nm to different total fluences (100 or 200 J/cm2; 50, 100 or 200 J/cm) at 5 or 15 min after intravenous administration of the drug (2 mg/kg). Areas on the bladder and colon were also irradiated. The local light fluence rate and temperature were monitored by interstitial probes in the prostate. All animals recovered well, without urethral complications. During the 1 week to 3 month post-treatment period, the prostates were harvested for histopathological examination. The PDT-induced lesions showed uniform hemorrhagic necrosis and atrophy, were well delineated from the adjacent normal tissue and increased linearly in diameter with the logarithm of the delivered light fluence. A maximum PDT-induced lesion size of over 3 cm diameter could be achieved with a single interstitial treatment. There was no damage to the bladder or rectum caused by scattered light from the prostate. The bladder and rectum were also directly irradiated with PDT. At 80 J/cm2, a full-depth necrosis was observed but resulted in no perforation. At 40 J/cm2, PDT produced minimal damage to the bladder or rectum. On the basis of optical dosimetry, we have estimated that 20 J/cm2 is the fluence required to produce prostatic necrosis. Thus, the normal structure adjacent to the prostate can be safely preserved with careful dosimetry. At therapeutic PDT levels, there was no structural or functional urethral damage even when the urethra was within the treated region. Hence, Tookad-PDT appears to be a promising candidate for prostate ablation in patients with recurrent, or possibly even primary, prostate cancer.

Topics: Animals; Bacteriochlorophylls; Dogs; Male; Models, Animal; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms