gdc-0449 and Hamartoma-Syndrome--Multiple

Oral vismodegib therapy and photodynamic therapy (PDT) are non-invasive treatments for basal cell carcinoma (BCC) with overlapping utility in widespread BCCs and patients who are poor surgical candidates. There is no published study to date investigating the combination use of PDT with vismodegib to optimize individual response rates.. To evaluate the combination of red light PDT and vismodegib therapy in patients with multiple nodular BCCs. The primary objective was to determine the safety of this combination therapy. Secondary outcomes included evaluation of the overall response rate, treatment-related pain, and cosmesis.. An open label pilot study of immunocompetent patients with multiple BCCs treated with 3 months of continuous vismodegib therapy (150 mg daily) and 3 consecutive ALA PDT sessions. Outcomes were assessed following each PDT session and 30 days post-treatment.. Four patients with multiple nodular BCC (median=5) were enrolled in the trial between January and August of 2016. Three patients completed the full intervention phase trial and a total of 19 lesions were treated. One patient completed 2 months of vismodegib and 2 PDT sessions. One PDT session was sufficient for small lesions, whereas larger lesions required all 3 sessions. The fifteen evaluable lesions at the end of the 3 PDT sessions showed complete responses. At 30-day follow-up, one of the treated lesions was noted to have clinical evidence of disease. Overall response rate showed 90% complete response and 10% partial response for the study. Combination therapy was well tolerated and yielded a similar or superior side effect profile to that of individual therapies with excellent cosmesis.. Combination PDT-vismodegib is a potential safe & effective therapy for the treatment of multiple BCCs that may enhance efficacy of individual therapies.

Topics: Aged; Aminolevulinic Acid; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Combined Modality Therapy; Hamartoma Syndrome, Multiple; Humans; Immunocompromised Host; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Pyridines; Skin Neoplasms

Vismodegib is indicated for the treatment of advanced or metastatic basal cell carcinoma (BCC). The predictive factors of response to vismodegib have so far been poorly described.. The primary objective was to determine the profile of patients responding to vismodegib and the duration of response. Secondary objectives were to assess whether there is a correlation between the duration of treatment and the risk of relapse, and to define factors associated with relapse.. We included 61 patients with locally advanced BCC (laBCC) or multiple BCC, treated with vismodegib (150 mg per day), from July 2011 to November 2015, in the Oncodermatology Department of Nantes University Hospital in France. Tumour response was assessed using Response Evaluation Criteria in Solid Tumours version 1.1.. Thirty-nine patients had advanced BCC (64%) and 22 patients multiple BCC (36%), including 10 patients with Gorlin syndrome. No factor predicted response to vismodegib. The median progression-free survival (PFS) was 69.5 months for the total population. In multivariate analysis, multiple BCC was the only factor associated with an increased risk of relapse (HR: 13.80 [CI95%, 1.93-98.64, p < 0.01]). Treatment duration decreased the risk of relapse (HR 0.95 [CI95%, 0.90-0.99, p = 0.0467]). Among the 20 patients who experienced relapse during follow-up, 15 (75%) were re-treated with vismodegib, with a response rate of 66%.. Although we were unable to establish predictive factors for the response to vismodegib, we demonstrate for the first time that increased treatment duration correlates with a decreased risk of relapse.

Topics: Anilides; Carcinoma, Basal Cell; Hamartoma Syndrome, Multiple; Humans; Neoplasm Recurrence, Local; Pyridines; Skin Neoplasms

Vismodegib has been used for the treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC (mBCC) since 2011. Most efficacy and safety data are provided by clinical trials. This study evaluates the effectiveness of vismodegib for the treatment of laBCC, mBCC and basal cell nevus syndrome (BCNS) patients, and the tumour characteristics associated with a higher probability of achieving a complete response in the Netherlands.. A retrospective cohort study that included all patients ≥18 years with histologically proven basal cell carcinoma that received ≥1 dose of vismodegib between July 2011 and September 2019 in the Netherlands.. In total, 48 laBCC, 11 mBCC and 19 BCNS patients were included. Median progression-free survival was 10.3 months (95% confidence interval (CI), 7.5-22.6) for laBCC, 11.7 (95% CI, 5.2-17.5) for mBCC and 19.1 (95% CI, 7.4-20.2) for BCNS. Larger laBCCs were associated with a lower probability of complete response (hazard ratio (HR) 0.77 per increase in cm, p = 0.02). Of all BCNS patients, 63% received ≥2 treatment sequences with vismodegib; all achieved partial responses.. Half of the aBCC patients progress within 1 year after the start of vismodegib treatment. More research is needed to investigate other treatment strategies after vismodegib progression and to evaluate long-term effects of repetitive vismodegib treatment.

Topics: Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Female; Follow-Up Studies; Hamartoma Syndrome, Multiple; Humans; Middle Aged; Pyridines; Retrospective Studies; Time Factors

Topics: Aged, 80 and over; Anilides; Basal Cell Nevus Syndrome; Biphenyl Compounds; Carcinoma, Basal Cell; Female; Hamartoma Syndrome, Multiple; Humans; Pyridines

Basal cell carcinoma (BCC) is the most common human malignant neoplasm. However, there are multiple BCC subtypes that share clinical features while demanding different management. We present a case of a woman with hundreds of BCCs throughout her body that were resistant to vismodegib and without other features of basal cell nevus syndrome. Histological results of biopsies taken from various sites revealed three lesions characteristic of infundibulocystic BCCs (IBCCs) and two BCCs. Paired whole-exome sequencing performed using DNA isolated from blood and one of her IBCCs uncovered a germline heterozygous

Topics: Aged; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Drug Resistance, Neoplasm; Female; Germ-Line Mutation; Hamartoma Syndrome, Multiple; Humans; Pyridines; Repressor Proteins

Topics: Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Hamartoma Syndrome, Multiple; Humans; Patient Reported Outcome Measures; Pyridines; Quality of Life; Skin Neoplasms

Vismodegib treatment of multiple basal cell carcinomas (BCCs) is limited by adverse effects and high relapse rates: intermittent regimens are therefore preferred for long-term administration. The objective of this study was to investigate clinical and dermoscopic changes in BCCs during long-term intermittent treatment and to identify those most indicative of tumor persistence/clearing. Clinical and dermoscopic images (n = 380 each) of 38 BCCs were acquired at 10 observation times (t0-t9). Biopsies were performed at baseline (t0) and after 72 weeks of treatment (t9). All images were evaluated retrospectively by experts who assessed the presence/absence of 12 clinical and 14 dermoscopic features: clinical scores (CScs) and dermoscopic scores (DScs) were then calculated.

Topics: Aged; Aged, 80 and over; Anilides; Carcinoma, Basal Cell; Hamartoma Syndrome, Multiple; Humans; Male; Middle Aged; Pyridines; Retrospective Studies

A female patient with xeroderma pigmentosum and multiple basal cell carcinomas was treated with a hedgehog pathway inhibitor (vismodegib), which successfully treated the majority of her basal cell carcinomas while preventing the appearance of new lesions. The sum diameter of lesions showed a 61% decrease after 16.5 months of treatment, although after 18.5 months of treatment, a persistent lesion showed progression and metatypical characteristics; adverse events included persistent alopecia muscle cramps, dysgeusia, and amenorrhea. Despite these limitations, vismodegib may have a role in the treatment of some patients with xeroderma pigmentosum.

Topics: Adult; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Female; Hamartoma Syndrome, Multiple; Humans; Pyridines; Skin Neoplasms; Xeroderma Pigmentosum

Topics: Anilides; Carcinoma, Basal Cell; Hamartoma Syndrome, Multiple; Photochemotherapy; Photosensitizing Agents; Pyridines