VAC chemotherapy with valproic acid for refractory/relapsing small cell lung cancer: a phase II study

Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study was to determine whether epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine and cyclophosphamide (VAC) regimen improves 6-month progression-free survival (PFS).Patients with pathologically proven SCLC refractory to prior platinum derivatives and etoposide were eligible. After central registration, patients received VAC plus daily oral valproic acid.64 patients were registered, of whom six were ineligible. Seven patients did not receive any CT, leaving 51 patients assessable for the primary end-point. The objective response rate was 19.6%. Median PFS was 2.8 months (95% CI 2.5–3.6 months) and 6-month PFS was 6%. Median survival time was 5.9 months (95% CI 4.7–7.5 months). Toxicity was mainly haematological, with 88% and 26% grade 3–4 neutropenia and thrombopenia, respectively.Despite an interesting response rate, the addition of valproic acid to VAC did not translate into adequate PFS in relapsing SCLC or SCLC refractory to platinum–etoposide.

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Phase II Study of Weekly Nanoparticle Albumin-Bound Paclitaxel as Second- or Third-Line Therapy in Patients with Advanced Non-Small Cell Lung Cancer

Chemotherapy ◽

10.1159/000508715 ◽

2020 ◽

Vol 65 (1-2) ◽

pp. 21-28

Author(s):

Mie Kotake ◽

Tomohito Kuwako ◽

Hisao Imai ◽

Yoshio Tomizawa ◽

Kyoichi Kaira ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Phase Ii Study ◽

Performance Status ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung

Introduction: Treatment outcomes in patients with advanced non-small cell lung cancer (NSCLC) are poor due to limited treatment options. Objective: We conducted a multicenter, single-arm phase II study to prospectively assess the efficacy and safety of weekly nab-PTX in patients with advanced NSCLC with failed cytotoxic chemotherapy. Methods: Patients with advanced NSCLC having adequate organ functions with a performance status of 0–1 were enrolled. A 100 mg/m2 dose of nab-paclitaxel was administered on days 1, 8, and 15 of a 28-day cycle. Primary endpoint was the objective response rate (ORR). Secondary endpoints were disease control rate (DCR), toxicity profile, progression-free survival (PFS), and overall survival (OS). Results: Between September 2013 and May 2016, 35 patients were enrolled. The ORR was 31.4%, and the DCR was 74.3%. The median PFS was 3.6 months, and the median OS was 11.4 months. The most common grade 3 or 4 toxicities included neutropenia (54.3%), leukopenia (42.9%), and anemia (11.4%). Two patients discontinued chemotherapy due to pneumonitis. Conclusions: Nab-PTX may be a later-line chemotherapeutic option for previously treated advanced NSCLC.

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Phase II study of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) in Korea.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.7_suppl.92 ◽

2017 ◽

Vol 35 (7_suppl) ◽

pp. 92-92

Author(s):

Keunchil Park ◽

Eun Kyung Cho ◽

Jin Hyoung Kang ◽

Ji-Youn Han ◽

Jong Seok Lee ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Phase Ii Study ◽

Objective Response ◽

Small Cell ◽

Stage Iiib ◽

Phase Iii ◽

Small Cell Lung

92 Background: Nivolumab (BMS-936558/ONO-4538), a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in several tumor types. Recently, two phase III studies (CheckMate-017 and -057) demonstrated that nivolumab improved overall survival (OS) than docetaxel in second-line of squamous (SQ) and non-squamous (NSQ) Non-Small Cell Lung Cancer (NSCLC), respectively. Here, we report the results of a phase II study to evaluate the efficacy and safety of nivolumab in Korean patients (pts) with previously treated advanced SQ and NSQ NSCLC. Methods: This study requires pts aged ≥ 20 years with ECOG Performance Status (PS) of 0 or 1, stage IIIB/IV or recurrent NSCLC and at least one prior chemotherapy including platinum containing regimen. Pts received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity. The primary endpoint in this study was the objective response rate (ORR) (RECIST v1.1). Results: Nivolumab was administered to 100 NSCLC pts (SQ: 44, NSQ: 56), male/female: 78 (SQ: 44, NSQ: 34)/22 (SQ: 0, NSQ: 22); PS 0/1: 14 (SQ: 6, NSQ: 8)/86 (SQ: 38, NSQ: 48); aged 29 to 80 [median: 66.5] years (SQ: 40 to 80 [median: 69.5], NSQ: 29 to 77 [median: 63.5]); Stage IIIB/IV/recurrence: 6 (SQ: 5, NSQ: 1)/91 (SQ: 37, NSQ: 54)/3 (SQ: 2, NSQ: 1)). In SQ and NSQ NSCLC, ORR was 15.9% (7/44) and 23.2% (13/56), respectively. Median progression-free survival was 2.6 mo and 5.3 mo, respectively. Complete Response was observed in 2.3% (1/44) and 1.8% (1/56), respectively. Median OS was 12.3 mo and 16.3 mo, respectively. Median follow-up was 8.9 mo and 12.3 mo, respectively. Most common adverse drug reaction (ADR) was decreased appetite 15.9% (7/44), followed by pyrexia 9.1% (4/44) in SQ NSCLC, and decreased appetite 12.5% (7/56), followed by pruritus 10.7% (6/56), fatigue 8.9% (5/56), pyrexia 5.4% (3/56) and nausea 5.4% (3/56) in NSQ NSCLC. Grade 3-4 ADR was observed in 6.8% (3/44) and 10.7% (6/56) of SQ and NSQ NSCLC, respectively. No interstitial lung disease and no grade 5 ADRs were observed in this study. Conclusions: Nivolumab was considered to be effective and used safely in Korean pts with SQ and NSQ NSCLC as well as in non-Korean pts with SQ and NSQ NSCLC. Clinical trial information: NCT02175017.

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Phase II study of oral fluoropyrimidine (UFT) plus vinorelbine in the elderly (age > 70) with advanced non-small cell lung cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18075 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18075-18075

Author(s):

H. Suyama ◽

Y. Shigeoka ◽

T. Igishi ◽

S. Matsumoto ◽

K. Yasuda ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Phase Ii Study ◽

Objective Response ◽

The Elderly ◽

Small Cell ◽

Small Cell Lung ◽

Platinum Based Chemotherapy

18075 Background: Many pts with non-small cell lung cancer (NSCLC) are in elderly population. There are few pts who can receive standard treatment with platinum-based chemotherapy because of their poor organ functions. Thus, the development of a low-toxic and highly- effective regimen is needed for these populations. We have reported schedule-dependent synergism of vinorelbine and 5-FU against NSCLC cell lines. Furthermore, we have already conducted phase I study using vinorelbine and UFT, and have decided the recommended dose of this regimen. Methods: The objective of this prospective phase II study was to assess the efficacy and toxicity of this regimen in the elderly. Chemonaive NSCLC stage IIIB or IV pts, aged 70 or more, with performance status 0/1 were enrolled in this study. The pts received a treatment consisting of 20mg/m2 of vinorelbine on days 1 and 8, followed by 600mg of UFT orally on days 2–6 and 9–13 every 3 weeks for more than 4 cycles. Results: Until April 24, 2006, of 30 pts enrolled in this study, 29 pts were evaluable. Median age was 78 (range 71–86) and median cycles of chemotherapy were 4 (1–32). Objective response rate was 27% (95% CI; 10–44%), median time to progression was 150 days (15–470) and median over all survival time was 270 days (77–892). Treatment-related toxicity were neutropenia G3 33%, G4 7%; febrile neutropenia G3 4%; pneumonia G3 10%. Conclusions: This data points out vinorelbine and UFT as an active and tolerable regimen in the elderly with advanced NSCLC. No significant financial relationships to disclose.

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ALTA-2: Phase II study of brigatinib in patients with ALK-positive, advanced non-small-cell lung cancer who progressed on alectinib or ceritinib

Future Oncology ◽

10.2217/fon-2020-1119 ◽

2021 ◽

Vol 17 (14) ◽

pp. 1709-1719

Author(s):

Edward S Kim ◽

Fabrice Barlesi ◽

Tony Mok ◽

Myung-Ju Ahn ◽

Junwu Shen ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Progressive Disease ◽

Phase Ii Study ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung ◽

Anaplastic Lymphoma

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved outcomes in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC). However, almost all patients eventually develop progressive disease on first-line ALK TKIs (e.g., crizotinib, alectinib and ceritinib). Brigatinib, a second-generation ALK TKI, may show efficacy in alectinib- and ceritinib-refractory ALK+ NSCLC. We describe the rationale and design of ALTA-2, a Phase II study of brigatinib in patients with locally advanced/metastatic ALK+ NSCLC and documented progressive disease on alectinib or ceritinib. The primary end point is confirmed objective response rate per independent review committee using response evaluation criteria in solid tumors version 1.1. Secondary end points include duration of response, progression-free survival, overall survival, safety and health-related quality of life.

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P2-210: Induction Therapy (IT) of non small cell lung cancer (NSCLC) with reliable response rate and low treatment related morbidity and mortality, a phase II study

Journal of Thoracic Oncology ◽

10.1097/01.jto.0000283918.72561.02 ◽

2007 ◽

Vol 2 (8) ◽

pp. S655

Author(s):

Kyu H. Shin ◽

Andrew Y. Soh ◽

Hiroshi Takita

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Induction Therapy ◽

Cell Lung Cancer ◽

Response Rate ◽

Phase Ii Study ◽

Small Cell ◽

Morbidity And Mortality ◽

Small Cell Lung

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Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.3.1068 ◽

1998 ◽

Vol 16 (3) ◽

pp. 1068-1074 ◽

Cited By ~ 113

Author(s):

S Kudoh ◽

Y Fujiwara ◽

Y Takada ◽

H Yamamoto ◽

A Kinoshita ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Overall Response Rate ◽

Response Rate ◽

Phase Ii Study ◽

Small Cell ◽

Small Cell Lung ◽

Overall Response

PURPOSE Irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC) as monotherapy. Cisplatin is also a key drug against SCLC. We conducted a phase II study of CPT-11 combined with cisplatin to evaluate the efficacy and toxicity of this regimen in patients with previously untreated SCLC. PATIENTS AND METHODS Seventy-five patients with previously untreated SCLC were enrolled onto the study. CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1 every 28 days. Four courses of chemotherapy followed by thoracic irradiation were given to patients with limited disease (LD) and six courses to patients with extensive disease (ED). RESULTS The overall response rate was 84%, with a complete response (CR) rate of 29%. Forty patients with LD achieved an overall response rate of 83% and a CR rate of 30% and 35 patients with ED achieved an overall response rate of 86% and a CR rate of 29%. The median response duration was 8.0 months for LD patients and 6.6 months for ED patients. The median survival was 14.3 months for LD patients and 13.0 months for ED patients. The major grade 3 or 4 toxicities were neutropenia (77%), leukopenia (45%), diarrhea (19%), and anemia (39%). Two patients died with concomitant neutropenia and diarrhea. CONCLUSION This is a new active regimen for SCLC, especially ED-SCLC, with acceptable toxicity. A phase III study that compares CPT-11/cisplatin with etoposide/cisplatin for ED-SCLC is now being conducted.

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Interim analysis of a phase II study of induction weekly paclitaxel/carboplatin regimens followed by maintenance weekly paclitaxel for advanced and metastatic non[ndash ]small cell lung cancer

Seminars in Oncology ◽

10.1053/sonc.2001.27610 ◽

2001 ◽

Vol 28 (4L) ◽

pp. 14-16

Author(s):

Chandra P. Belani

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Interim Analysis ◽

Phase Ii Study ◽

Small Cell ◽

Weekly Paclitaxel ◽

Small Cell Lung

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Faculty of 1000 evaluation for A phase II study of bevacizumab and erlotinib as initial treatment for metastatic non-squamous, non-small cell lung cancer with serum proteomic evaluation.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.717976259.793472648 ◽

2013 ◽

Author(s):

James Spicer

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Initial Treatment ◽

Phase Ii Study ◽

Small Cell ◽

Small Cell Lung

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Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.5.1948 ◽

1998 ◽

Vol 16 (5) ◽

pp. 1948-1953 ◽

Cited By ~ 60

Author(s):

J Zalcberg ◽

M Millward ◽

J Bishop ◽

M McKeage ◽

A Zimet ◽

...

Keyword(s):

Lung Cancer ◽

Phase Ii ◽

Advanced Nsclc ◽

Response Rate ◽

Phase Ii Study ◽

Performance Status ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung ◽

Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

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