A randomized phase II study to assess the effect of adjuvant immunotherapy using α-GalCer-pulsed dendritic cells in the patients with completely resected stage II–IIIA non-small cell lung cancer: study protocol for a randomized controlled trial

Abstract

BackgroundAs the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival.The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II–IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only).MethodsSubsequent to the complete resection of NSCLC, followed by the administration of cisplatin plus vinorelbine dual-agent combination adjuvant chemotherapy, patients who satisfy the inclusion criteria will be randomly allocated to either the α-GalCer-pulsed DC immune therapy group, or the standard treatment group.In total, 56 patients will be included in the study. The primary endpoint is recurrence-free survival, and the secondary endpoints are natural killer T-cell-specific immune response, the frequency of toxic effects and safety, and overall survival.DiscussionIn order to determine the efficacy of α-GalCer-pulsed DC therapy, the present study compares patients with stage II–III NSCLC who underwent complete surgical resection followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to those who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only).Trial registrationUMIN000010386 (R000012145). Registered on 1 April 2013.UMIN-CTR is officially recognized as a registration site which satisfies ICMJE criteria.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2103-4) contains supplementary material, which is available to authorized users.

Trial watch: dendritic cell vaccination for cancer immunotherapy

“…The majority of these studies (Figure 1) tested autologous DCs pulsed with: TAAs or peptides thereof, [325][326][327][328][329][330][331][332][333][334][335][336][337][338][339][340][341][342] autologous cancer cell lysates, [343][344][345][346][347][348] or TAA-coding RNAs. 276,[349][350][351][352] The predominant use of these TAA sources for the generation of DC-based vaccines is in line with previous trends, as documented in our previous Trial Watch on this subject, 279 de facto reflecting a broad consensus in the field.…”

“…While most of these clinical studies were basket trials enrolling patients with multiple solid tumors (Figure 1), 326,331,336,348 studies focusing on single indications most commonly enrolled patients with melanoma, 332,337,339,343 prostate cancer, 276,325,329,353 or glioblastoma (GBM). 341,346,350,352 This was followed by pancreatic cancer, 327,333,358 non-small cell lung carcinoma (NSCLC), 338,340,354 and myeloma 330,334,345 (Figure 1). This trend was very similar to the one we described in 2017, 279 with the single exception of studies enrolling subjects with renal cell carcinoma (RCC), which declined over the past 2 years.…”

“…In most clinical studies, DC vaccines were administered in combination with standard-of-care 348 or off-label chemotherapeutics (e.g., gemcitabine, cyclophosphamide, S-1, temozolomide, carboplatin, paclitaxel or docetaxel), 276,[326][327][328]337,338,341,344,346,350,358 radiotherapy, 335,341,346 targeted anticancer agents (e.g., tyrosine kinase inhibitors), 328,344 or specific immunotherapeutic regimens, including recombinant colony stimulating factor 2 (CSF2, best known as GM-CSF), recombinant IL2, ACT, and TL3 agonists. 326,333,344,352,353 Importantly, the vast majority of these clinical studies confirmed that DC-based vaccines are safe for cancer patients, 359 causing mild-to-moderate side effects including fever, erythema, flu-like symptoms, rash and/or fatigue, in a small proportion of patients.…”

Aerosol Immunotherapy with or without Cisplatin for metastatic lung cancer non-small cell lung cancer disease: In vivo Study. A more efficient combination

“…Nowadays there are ongoing studies were immunotherapy combinations are being studied and moreover; chemotherapy plus immunotherapy. 29 - 31 Another issue that has to be addressed is whether radiotherapy treatment prior to immunotherapy administration has a favorable synergistic effect for immunotherapy. 32 Indeed current data indicate that administration of radiotherapy enhance immunotherapy treatment, however; the time and dose of radiotherapy administration are yet to be clarified.…”

Reporting quality of randomized, controlled trials evaluating immunotherapy in lung cancer

“…For example, we used the OQS scoring method used in some quality evaluation articles, as well as all the entries in the 28 CONSORT statements in some quality evaluation articles. Compared with other quality evaluation articles, our article is more comprehensive and advanced 35‐53 …”