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Background: Adoptive immunotherapy for cancer has evolved through development of novel technologies for generating a large number of activated killer cells, such as αβ T-cells, γδ T-cells, and natural killer cells. There has been no prospective trial of combination therapy involving adoptive immunotherapy and first-line chemotherapy for stage IV colorectal cancer. The present pilot study aimed to evaluate the safety and feasibility of combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer (COMVI study)., Patients and Methods: The COMVI study was a prospective, single-arm pilot trial. Therapy in each 21-day treatment cycle involved XELOX (130 mg/m 2 of oxaliplatin on day 1 plus 1,000 mg/m 2 of capecitabine twice daily on days 1-14), bevacizumab (7.5 mg/kg on day 1), and αβ T-lymphocytes (over 5×10 9 on day 18) cultured ex vivo with an immobilized antibody to CD3 and interleukin-2., Results: The study included six patients (two men and four women) between June 2013 and September 2014. The median patient age was 68 years (range=55-75 years). The overall response rate was 83.3% [complete response in two (33.3%); partial response in three (50.0%); stable disease in one (16.7%); no cases of progressive disease]. The tumor volume reduction rate was 53% (range=38.0-100%). The median progression-free and overall survival durations were 567 and 966 days, respectively. Most adverse events were mild-to-moderate in intensity, and no grade 4 adverse events occurred in the six patients. Only one patient experienced grade 3 hypertension and ileus. Immunotherapy-associated toxicity was minimal in this study., Conclusion: Combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer is feasible and safe. Phase II prospective studies are needed to confirm the safety and efficacy of such chemoimmunotherapy., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

From 1983 to 1988, 20 patients (group A: 3 stage T1, 4 stage T2 and 13 stage T3-4 tumors) with bladder cancer were treated with single injection of CDDP (150-200 mg/body), and 28 patients (group B: 4 stage T1, 9 stage T2 and 15 stage T3-4 tumors) were treated twice with injection of CDDP (100 mg/m2) and THP-ADM (40 mg/m2) mixture from the internal iliac artery. As a rule, one half of the agents was equally given for the both sides, while 75% dose was given to the tumor side to the case with unilateral localized tumors. Then total or partial cystectomy was followed. When residual invasive cancer was pathologically present in operative specimens, patients underwent three to six courses of adjuvant chemotherapy including CDDP. Clinical response rate (CR+PR) to the intra-arterial chemotherapy in group A and B were 39% and 62%, respectively. Pathological response rate (grade 3 and grade 4 by Oboshi and Shimozato classification) were 17% in both group. After total cystectomy, the 2-year cancer specific survival rates of 17 patients in group A and 22 patients in group B were 75% and 59%, respectively. The 2-year cancer specific survival rates of 8 patients in group A and 10 patients in group B with pT3b were 63% and 54%, respectively. No cancer death occurred thereafter in the patients of group A during another three years. The 3-year cancer specific survival rate of 9 patients after partial cystectomy (3 in group A, 6 in group B) was 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

During 2 years and 10 months from November 1985 to September 1988, 50 patients with invasive bladder cancer (pT2-4, pN0-2, M0) were treated with total cystectomy followed by adjuvant combination chemotherapy including cis-platinum. In addition, so-called immunopotentiator (OK-432) and Kanpo (Juzentaihoto: TJ-48) were given to the patients in a random fashion to evaluate whether or not these agents had any significant effect on patients' prognosis. The 3- and 5-year survival rates for 48 evaluable patients were 71% and 67%, respectively. Histologic grade of primary tumors and number of cycles of adjuvant chemotherapy administered had a significant correlation to patients' survival: patients with grade 2 anaplasia had a better 3- and 5-year survival rates than those with grade 3 anaplasia, and patients receiving 3 or more cycles of chemotherapy had a better 3-year survival rate than those with 2 or less cycles. pT and pN categories also affected patients' survival, though not statistically significant. Administration of OK-432 or TJ-48 and pre-operative treatment such as irradiation and intra-arterial chemotherapy had no favourable effects on the survival. Side effects of the adjuvant chemotherapy were minimal to moderate and more than 70% of the patients tolerated at least 3 cycles of chemotherapy. It is likely that adjuvant chemotherapy, when given in a post-operative setting, should be repeated at least 3 cycles or more.

Thirteen patients with advanced testicular tumors (seminoma 2, non-seminoma 11) were treated with combination chemotherapy involving BLM, vinca alkaloid and CDDP (BVP) as induction therapy and followed with CPM, VCR and CDDP as maintenance therapy. BVP and COP administration was repeated every 3 and 4 to 8 weeks for 1 year, if there were no serious side effects. The overall response rate (CR + PR) was 92% with a 69% CR rate. At a mean follow-up of 30 months (7-52 month range), 54% of the patients were alive with no evidence of disease. Bulky metastases, failure to respond to prior chemotherapy and teratomatous metastases were considered to be poor prognostic factors. The toxicity of BVP was similar to that reported for CDDP, except that allergic reaction occurred in 3 patients after several courses of treatment. Two of the 3 went into anaphylactic shock.

Ten patients with Stage I non-seminomatous germ cell testicular tumors underwent orchiectomy and combination chemotherapy with bleomycin, vincristine and methotrexate with CF rescue (BOM) as an induction therapy followed by cyclophosphamide, vincristine and methotrexate as a maintenance therapy (COM). The results were as follows: BOM seemed to be effective as a further treatment for Stage I non-seminomatous germ cell testicular tumor patients. All 10 patients are alive and disease-free for a period from 1 year and 6 months to 5 years and 3 months (mean: 3 years and 9 months). The chemotherapy should be continued at least for a year, since relapse occurred in 2 of 4 patients who received only induction therapy. However, they completely responded to other chemotherapy regimens (BVP and BOAM ). BOM and COM therapy were scarcely toxic and no serious side effects were recognized. From the above results, it was considered that combination chemotherapy (BOM and COM) can be an alternative treatment to the conventional retroperitoneal node dissection and radiation therapy for Stage I non-seminomatous germ cell tumors.