Photodynamic therapy for lung cancer

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A; GONZALEZ, L

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2012 p. 1 - 30

1668-2793

Lung cancer is the most commonly diagnosed tumor and the main cause of death worldwide. In 2008, it represented 13% of all the diagnosed tumors (1.6 million) and resulted in 18% of deaths (1.8 million) worldwide. In 2010, more than 58,000 subjects died due to tumors in Argentina, lung cancer accounting for approximately 15% of deaths.Advances in early diagnosis have led to achieve detection at an early stage. Approximately 70% of subjects require lobectomy and the remaining 30% require a major resection with curative intent. The rate of cure after resection at early stages is above 70% with calculated survival after 5 years of 50% (from 73% in stage pIA to 58% in pIB). Unfortunately, 85% have advanced stage disease at diagnosis and another high percentage is excluded from surgery due to comorbidities. At present, there are at least five techniques available used to ablate malignant lesions at the endobronchial level which are an alternative to surgery; they include photodynamic therapy (PDT) which is proposed for the treatment of tumors in the airways and lungs at inoperable early stages and for palliation of the symptoms in advanced cases of bronchial obstruction.TechnologyPTD involves the initial marking of pathological tissue using an intravenous photosensitizer agent and later a tissue destruction process, by exposing it to a light source with a specific wavelength. This triggers the production of reactive oxygen molecules and a cascade of events leading to neoplastic cell destruction. There are 12 molecules used as photosensitizers worldwide, four of them (porfimer sodium, Temoporfin, HPPH, Talaporfin) are used in lung cancer.PurposeTo assess the available evidence on the efficacy, safety and coverage policy related aspects on the use of photodynamic therapy in patients with lung cancer.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsOne systematic review which included seven RCTs, thirteen case series, six clinical practice guidelines and seven coverage policies were included.One series published in 2006, at early stages and with curative intent, on 204 patients, with a rate of complete response to ablate tumor tissue of 85% in 204 patients, and another one published in 1998 with similar results are identified. Another series on 75 cases which achieved response rates above 90% by using a second generation photosensitizer was published in 2010. The survival reported after 5 years ranged from 43% to more than 80% in the most recent series.At advanced stages, one narrative review including seven RCTs was published in 2010. Two of them (52 patients) assessed PDT with radiotherapy. One significant difference was found in recurrence-free time (233 days for PDT plus radiotherapy vs. 107 days for radiotherapy alone, p<0.01), as well as the rate of improvement for dyspnea or hemoptisis. No evidence was found when assessing mortality rates or global survival. Other three clinical trials (198 patients) compared PDT vs. laser ND:YAG. Only in one of them, survival was significantly higher in the PDT group (265 days vs. 95 days, p<0.01). When assessing symptomatic relief, PDT showed effectiveness in reducing dyspnea by 30% and major airway obstruction by more than 50%, as shown in a series on 211 patients published in 1998. Survival seems to be closely related to the patient performance status (PS), achieving a survival rate close to 50% after 2 years those who had a PS less than or equal to 2, and just 3.7% those patients with a PS above 2.Several international agencies, in their clinical practice guidelines, describe PDT as one of the choices for curative or palliative treatment in those patients where surgery is contraindicated.No economic evaluations were found in relation to the studied technology. The total cost of PDT including the photosensitizer and professional fees would exceed 110,000 Argentina pesos. Several United States health sponsors agree on approving PDT for patients with lung cancer who are not eligible for surgery or radiotherapy at early stages or as curative treatment or with the purpose of palliating symptoms when endobronchial obstruction is present.ConclusionsThe evidence found was of low to intermediate quality, consistent with the few RCTs with methodological defects and uncontrolled case series found.PDT seems to be effective when used with curative intent at early stages of lung cancer; showing an effectiveness in neoplastic lesion ablation that ranged from 30 to 100% according to different studies. At advanced stages with palliative intent, PDT seems to be effective in reducing dyspnea with a 30% improvement rate. In this context, it would be more effective in combination with radiotherapy in increasing the rate of symptomatic relief and prolonging the length of response.However, the groups under study had significant baseline differences that may have clearly influenced the results. Even though the method shoes a lower morbidity than its alternatives and it may be used in patients with complex medical conditions, its common adverse effects may limit its use. It is necessary to conduct comparative studies among the different treatments with long-term result measurements in order to make definite recommendations about the role of PDT in the treatment of lung cancer.