Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for advanced non-small-cell lung cancer

Cappuzzo, Federico; Novello, Silvia; Marinis, Filippo de; Franciosi, Vittorio; Maur, M; Ceribelli, Anna; Lorusso, Vito; Barbieri, Fausto; Castaldini, Luciano; Crucitta, E.; Marini, Luca; Bartolini, Stefania; Scagliotti, Giorgio V.; Crinò, Lucio

doi:10.1038/sj.bjc.6602667

Cited by 29 publications

(19 citation statements)

References 35 publications

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“…More than 85% of lung cancer patients are diagnosed with non-small cell lung cancer (NSCLC). Most NSCLC patients are diagnosed at an advanced stage, with most patients having stage III or IV disease, for which the 5-year survival rates are <15% [1,2,3]. …”

Section: Introductionmentioning

confidence: 99%

Phase II Trial of Biweekly Chemotherapy with Docetaxel and Cisplatin in High-Risk Patients with Unresectable Non-Small Cell Lung Cancer

Kim

Kang

et al. 2013

Chemotherapy

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Purpose: We investigated the efficacy and toxicity of a biweekly schedule of docetaxel and cisplatin in high-risk patients with unresectable (stages IIIB-IV) non-small cell lung cancer (NSCLC). Methods: In this study, 48 high-risk patients with previously untreated locally advanced or metastatic NSCLC were treated with combination chemotherapy consisting of docetaxel 40 mg/m² and cisplatin 40 mg/m²; both drugs were given biweekly, on days 1 and 15, every 4 weeks in an outpatient setting. Results: Complete response, partial response, and stable disease were observed in 1 (2.1%), 30 [62.5%, 95% confidence interval (CI) 47.9-77.1], and 4 (8.3%) patients. The median overall survival was 15.1 months (95% CI 11.7-18.5) and the median time to progression was 7.5 months (95% CI 6.4-8.6). The major toxicity was grade 3 anemia in 7 (14.6%) patients. Grade 3/4 neutropenia was observed in 5 (10.4%) patients. Among the nonhematologic toxicities, grade 3 infection and grade 3 diarrhea were observed in 5 (10.4%) and 4 (8.3%) patients, respectively. No treatment-related mortality was found. Conclusions: As a front-line chemotherapy for high-risk patients with unresectable NSCLC in an outpatient setting, the biweekly schedule of docetaxel and cisplatin showed feasible efficacy with acceptable hematologic toxicities, comparable to the results of previous studies of triweekly or weekly schedules. Additional large randomized studies are needed to optimize the schedule and dosage of combination therapy with docetaxel and cisplatin in high-risk patients with unresectable NSCLC.

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Section: Introductionmentioning

confidence: 99%

Phase II Trial of Biweekly Chemotherapy with Docetaxel and Cisplatin in High-Risk Patients with Unresectable Non-Small Cell Lung Cancer

Kim

Kang

et al. 2013

Chemotherapy

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“…OHP is part of the standard treatment of colon cancer and cisplatin of NSCLC; there is some evidence of clinical activity of the combination of OHP and gemcitabine in NSCLC (19)(20)(21)(22). This indicates that the …”

Section: Discussionmentioning

confidence: 99%

“…Oxaliplatin is used in the treatment of colorectal cancer (15). Gemcitabine combined with cisplatin is one of the most active combinations in NSCLC (16) for which very pronounced synergism was found for in vitro and in vivo combinations with gemcitabine-cisplatin (17,18) and gemcitabine-oxaliplatin (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Cell cycle effects of fatty acid derivatives of cytarabine, CP-4055, and of gemcitabine, CP-4126, as basis for the interaction with oxaliplatin and docetaxel

Peters¹

2009

Int J Oncol

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Abstract. To bypass resistance due to limited entry into the cell derivatives of cytarabine (CP-4055, elacytarabine) and gemcitabine (CP-4126) containing a fatty acid chain at the 5' position of the nucleoside were developed. CP-4055 showed an increased retention of the active metabolite, the triphosphate. This characteristic was supposed to favor combinations, such as with the tubulin antagonist docetaxel, the platinum oxaliplatin and the antifolate pemetrexed. The role of the cell cycle effects of CP-4055 and CP-4126 on the efficacy of the combination with docetaxel or pemetrexed was determined. The combination of CP-4055 with oxaliplatin and docetaxel was also evaluated in a mouse xenograft model. CP-4055 induced a G2/M and S phase accumulation and CP-4126 an S phase accumulation. Both analogs induced a dose-dependent cell kill (apoptosis and necrosis). None of the docetaxel combinations induced a synergistic effect. The combination of docetaxel with CP-4055 or CP-4126 induced a G2/M accumulation in the A549 (lung cancer) cell line, but a G0/G1 accumulation in the WiDR (colon cancer) cell line. Preincubation with docetaxel induced an increased cell kill in both cell lines. The combination with oxaliplatin showed a synergistic effect in both cell lines. Combinations with pemetrexed were antagonistic in both cell lines. In the A549 cell line pemetrexed with CP-4055 led to an increase of the G0/G1 phase and the S phase. In WiDR the combination of pemetrexed with CP-4055 increased the G0/G1 phase and increased the cell kill. Pemetrexed with CP-4126 induced an increase in the G0/G1 phase and the S phase in the A549 cell line. In the xenograft study, on a colon cancer and a lung metastasis model, the combination of CP-4055 with docetaxel showed the best results. Treatment with CP-4055 followed by docetaxel after 4 h resulted in a reduction in metastasis in a lung metastasis model, and a favorable toxicity profile was observed. In conclusion, the combinations with oxaliplatin showed a synergistic effect in the combination studies. Although the combinations with docetaxel did not show an enhanced effect in the in vitro studies, this combination revealed an increased effect in the xenograft model.

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“…About 54% of patients present a metastasis at diagnosis due to lack of clinical symptoms at early stages, which tend to result in an extremely poor prognosis with an overall 5-year survival rate of 3.8% [3]. For most advanced lung cancers, standard chemotherapy generally is the mainstream of management involving Pemetrexed [14][15], Oxaliplatin [16] and Docetaxel [17], but apparently it has reached a plateau with disappointing outcomes [18]. Despite the introduction of a series of targeted drugs for patients with epidermal growth factor receptor (EGFR) mutations (Gefitinib or Erlotinib) [19][20] and ALK rearrangement (Crizotinib) [20] in the past decade, the survival rate still has not been significantly improved.…”

Section: Discussionmentioning

confidence: 99%

Hapten Improved Overall Survival Benefit in Late Stages of Non-Small Cell Lung Cancer (NSCLC) by Ultra-Minimum Incision Personalized Intratumoral Chemo Immunotherapy (UMIPIC) Therapy With and without Radiation Therapy

Yu¹

2016

JCPCR

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Aims: To evaluate overall survival time of hapten-enhanced chemo immunotherapy in the treatment of advanced NSCLC by UMIPIC with and without radiation therapy and to analyze the effective of hapten as an immune booster. Materials and Methods:298 patients with advanced NSCLC were treated with UMIPIC or Intratumoral chemotherapy (ITCT). Some in both groups had also received radiation therapy prior to UMIPIC or ICTC. UMIPIC (86 cases) was delivered intratumorally in combination with a proprietary therapeutic regimens composed of four components including an oxidant, two cytotoxic drugs and a hapten, UMIPIC-R (115 cases) with the same procedures and added common radiation therapy. ITCT was applied the same procedures and regimens only without the hapten, ITCT-R with same procedures as ITCT and added common radiation therapy. All data from four groups were reviewed and analyzed. 201 of NSCLC patients were treated with UMIPIC, 86 of 201 NSCLC had radiation therapy, and 97 of NSCLC patients with ITCT, 48 of 97 NSCLC had radiation therapy. All patients were followed until their death and survival benefits were analyzed. Some biopsies were taken for immunohistochemical staining and observation under electronic microscopy.Results: Median survival time (OS) was 20 months in UMIPIC (test) and 7 months in ITCT (control) (P <0.001) and 6-months and 1-year year survival rate of the UMIPIC and ITCT were 95.3% vs. 61.6% (P <0.001) and 86 % vs. 32.7% (P <0.001), 2-years survival rate of the UMIPIC and ITCT were 37.2% vs. 6.5% (P <0.01) respectively. For groups with radiation therapy, median survival time (OS) was 16 months in UMIPIC-R (test with radiation therapy) and 7 months in ITCT-R (control with radiation therapy) (P<0.05), 6-months and 1-year year survival rate of the UMIPIC-R and ITCT-R were 97.4% vs. 62.5% (P<0.001) and 76.5% vs. 37.5% (P <0.001), 2-years survival rate of the UMIPIC-R and ITCT-R were 36.5% vs. 18.8% (P <0.05) respectively. Also it was revealed that dendritic cells and CD4+, CD8+ in the immunohistochemical staining and observation in EM (Figure 4), further confirmed more activities of immunological response induced by UMIPIC. Conclusion:Hapten improved clinical survival benefits by UMIPIC with hapten and double cytotoxic drugs conferred a superior survival time for patients with advanced NSCLC compared to ITCT with or without multi fractional radiation therapy. The addition of the hapten in UMIPIC with double drugs demonstrated a significant improvement in terms of prolonged survival time.

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Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for advanced non-small-cell lung cancer

Cited by 29 publications

References 35 publications

Phase II Trial of Biweekly Chemotherapy with Docetaxel and Cisplatin in High-Risk Patients with Unresectable Non-Small Cell Lung Cancer

Phase II Trial of Biweekly Chemotherapy with Docetaxel and Cisplatin in High-Risk Patients with Unresectable Non-Small Cell Lung Cancer

Cell cycle effects of fatty acid derivatives of cytarabine, CP-4055, and of gemcitabine, CP-4126, as basis for the interaction with oxaliplatin and docetaxel

Hapten Improved Overall Survival Benefit in Late Stages of Non-Small Cell Lung Cancer (NSCLC) by Ultra-Minimum Incision Personalized Intratumoral Chemo Immunotherapy (UMIPIC) Therapy With and without Radiation Therapy

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