Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer

Abstract

Objective

Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population.

Materials and methods

The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively.

Results

No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p < 0.0018). Twelve patients who continued immunotherapy with the second cycle had a median PSADT of 58 months that remained stable after the second cycle. In the peripheral blood, specific PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment.

Summary

Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

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Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer

Abstract

Objective

Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population.

Materials and methods

The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively.

Results

No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p < 0.0018). Twelve patients who continued immunotherapy with the second cycle had a median PSADT of 58 months that remained stable after the second cycle. In the peripheral blood, specific PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment.

Summary

Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

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Rectal Cancer in Asian vs. Western Countries: Why the Variation in Incidence?

Opinion statement

Colorectal cancer (CRC) is the third most common cancer worldwide. CRC has been thought to be less common in Asia compared to Western countries. However, the incidence rates of CRC in Asia are high and there is an increasing trend in the Asian population. Furthermore, colorectal cancer accounts for the greatest number of all incidences of CRC in Asia. The increasing adoption of a Western lifestyle, particularly in dietary habits, is likely the most important factor contributing to the rapid increase in colon cancer incidence; it is noteworthy that trends for rectal cancer were flat. The etiology of colon and rectal cancer is a bit different. The risks of distal colon and rectal cancers are more likely to be related to environmental factors, such as polluted surface water sources, alcohol consumption, and habitual smoking. The lack of great change in the incidence of rectal cancer might be due to weaker associations with such lifestyle factors. Therefore, it has been hypothesized that proximal and distal sections of the colon and rectum are two different organs in terms of function and genetic background. It may mean differences in differential sensitivities and exposures to carcinogens. However, despite the decrease in whole incidence, the CRC incidence in young adults in Western countries are reversely increasing, especially in rectal cancer, due to reasons largely unknown. Although the treatment algorithm is different between Asia and western countries, globally, the survival rate for patients with rectal cancer has risen during the past 10 years. Screening contributes a great deal to reducing the incidence and improving survival. Most countries in Asia, such as China, need nationwide registration and screening systems to provide better data.

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Rectal Cancer in Asian vs. Western Countries: Why the Variation in Incidence?

Opinion statement

Colorectal cancer (CRC) is the third most common cancer worldwide. CRC has been thought to be less common in Asia compared to Western countries. However, the incidence rates of CRC in Asia are high and there is an increasing trend in the Asian population. Furthermore, colorectal cancer accounts for the greatest number of all incidences of CRC in Asia. The increasing adoption of a Western lifestyle, particularly in dietary habits, is likely the most important factor contributing to the rapid increase in colon cancer incidence; it is noteworthy that trends for rectal cancer were flat. The etiology of colon and rectal cancer is a bit different. The risks of distal colon and rectal cancers are more likely to be related to environmental factors, such as polluted surface water sources, alcohol consumption, and habitual smoking. The lack of great change in the incidence of rectal cancer might be due to weaker associations with such lifestyle factors. Therefore, it has been hypothesized that proximal and distal sections of the colon and rectum are two different organs in terms of function and genetic background. It may mean differences in differential sensitivities and exposures to carcinogens. However, despite the decrease in whole incidence, the CRC incidence in young adults in Western countries are reversely increasing, especially in rectal cancer, due to reasons largely unknown. Although the treatment algorithm is different between Asia and western countries, globally, the survival rate for patients with rectal cancer has risen during the past 10 years. Screening contributes a great deal to reducing the incidence and improving survival. Most countries in Asia, such as China, need nationwide registration and screening systems to provide better data.

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Le statut MSI est un biomarqueur prédictif de la chimioradiothérapie néoadjuvante pour adénocarcinome du rectum

Publication date: October 2017
Source:Cancer/Radiothérapie, Volume 21, Issues 6–7
Author(s): N. Meillan, D. Vernerey, G. Manceau, J. Lefèvre, J.-M. Simon, J.-B. Bachet, F. Huguet
Objectif de l'étudeLe phénotype MSS/MSI (MSS : absence d'instabilité des microsatellites ; MSI : instabilité des microsatellites) a un impact pronostique dans les cancers colorectaux de stade II–III avec un moindre risque métastatique pour le statut MSI. Son impact prédictif sur la réponse à la chimiothérapie et à l'immunothérapie est établi. Celui sur la réponse à la radiothérapie est inconnu. Cette étude avait pour objectif d'évaluer l'impact du statut MSI sur la réponse à la radiothérapie néoadjuvante des cancers du rectum localement évolués.Matériel et méthodeNous avons analysé rétrospectivement les dossiers de 17 patients avec le statut MSI et 338 patients avec celui MSS, atteints de cancer de stade T3–T4 et/ou avec atteinte ganglionnaire, pris en charge par chimioradiothérapie néoadjuvante de 45 à 50Gy en cinq semaines avec une chimiothérapie à base de fluoropyrimidines ou 25Gy en cinq fractions. Ces patients ont été appariés sur l'âge et le stade tumoral à l'aide d'un score de propension. Le critère de jugement principal était la réduction du stade T et/ou N sur la pièce opératoire après traitement néoadjuvant.RésultatsLe suivi médian était de 36,7 mois. Il y avait parmi les patients avec le statut MSI, deux tumeurs ypN+ (12 %), huit ypT1-2N0 (47 %) et sept ypT3-4N0 (41 %) contre respectivement 106 (31 %), 130 (38 %) et 102 (30 %) avec le statut MSS. Une réduction du stade tumoral a été observé chez 14 patients avec le statut MSI (93,3 %) contre 200 avec le statut MSS (59,2 %) (odds ratio [OR] : 0,10 ; intervalle de confiance à 95 % [IC 95 %] : 0,01–0,80, p=0,029). Le taux de rechute locale n'était pas significativement différent entre les deux populations, une patiente avec le statut MSI (7,7 %) contre 24 avec celui MSS (7,2 %) (OR=0,93 ; IC 95 % : 0,12–7,43, p=0,94), de même que la survie globale (hazard ratio [HR] : 0,39 ; IC 95 % : 0,05–2,87, p=0,35).ConclusionLe dysfonctionnement somatique du système de réparation des mésappariements de l'ADN semble entraîner une meilleure réponse à la radiothérapie néoadjuvante des cancers du rectum localement évolués. Cet impact ne se traduit pas significativement par un bénéfice en termes de rechute locale ni de survie globale avec un suivi médian relativement court.



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Issue Contents

Publication date: October 2017
Source:Cancer/Radiothérapie, Volume 21, Issues 6–7





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Nouvelles techniques dans le cancer de la prostate localisé : chirurgie et radiothérapie

Publication date: October 2017
Source:Cancer/Radiothérapie, Volume 21, Issues 6–7
Author(s): L. Cormier, G. Créhange
La prise en charge chirurgicale du cancer de la prostate localisé a été marquée ces dernières années par la place prépondérante de la surveillance active dans les formes de cancer à faible risque. En effet, le recul et la qualité des résultats sont maintenant suffisants pour proposer cette option à des patients relativement jeunes. En revanche, la question reste posée pour les formes intermédiaires. De plus, une extrême vigilance est indispensable pour la qualité de la sélection et du suivi des patients pour la surveillance active. Une autre évolution est l'importance prise par l'assistance robotique dans la prostatectomie totale. Même si le niveau de preuve en faveur du robot reste faible, son utilisation de plus en plus universelle est un fait indéniable qui répond vraisemblablement à la difficulté chirurgicale de cette intervention. Enfin, le concept du traitement focal du cancer de la prostate est en pleine évolution, sans doute lié à la qualité de l'IRM et la précision des biopsies de la prostate. Actuellement, le traitement focal du cancer de la prostate ne doit se faire que dans le cadre de la recherche clinique et/ou peut être par le biais de registres nationaux et validés par les différents acteurs intervenant dans la prise en charge des patients.The management of localized prostate cancer has been marked over these last years by the importance of Active Surveillance for low risk forms. Indeed, the long follow-up and the quality of the results are now sufficient to offer this option even in relatively young people. However, the question is still under investigation concerning intermediate risk of prostate cancer. Patients' selection and follow-up management are of very high importance. Another major evolution is the robotic assistance for radical prostatectomy. Even if the level of evidence is still low, the global utilization all over the world of robotic assistance is a major fact of these last years mostly explained by the difficulty to correctly perform manual laparoscopic surgical procedure. Lastly, the focal therapy of prostate cancer is a new concept. The development of this approach is authorized by the improvement of the quality of prostate MRI and the accuracy of prostate biopsy. Presently, the focal treatment has to be performed in clinical trials or maybe with the help of national database validated by all the actors concerned by the treatment of prostate cancer.



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