Efficacy of nanoparticle albumin-bound paclitaxel regimens for relapsed small cell lung cancer

Naito, Yujiro; Tamiya, Akihiro; Tamiya, Motohiro; Kimura, Yuri; Hamaguchi, Maki; Saijo, N.; Kanazu, Masaki; Tokura, Sayoko; Shiroyama, Takayuki; Morisita, Naoko; Omachi, Naoki; Suzuki, Hidekazu; Okamoto, Norio; Okishio, Kyoichi; Hirashima, Tomonori; Atagi, Shinji

doi:10.1097/md.0000000000007884

Cited by 17 publications

(21 citation statements)

References 22 publications

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“…These data confirmed the unfavourable prognostic role of CNS involvement, especially in relapsed SCLC. Our results were similar to those reported from a retrospective study 18 in which 9 of the 14 enrolled patients were treated with nab-paclitaxel, as third-line or later. In this subgroup, ORR, mPFS and mOS were 11%, 2.0 months and 4.0 months, respectively.…”

Section: Discussionsupporting

confidence: 90%

“…Three Asian retrospective analyses conducted in relapsed SCLC patients showed some anti-cancer activity of nab-paclitaxel. [18][19][20] Since nab-paclitaxel has not been prospectively studied in relapsed SCLC yet, we designed this open-label, prospective Phase 2 trial with the aim to assess its activity and safety in patients with both refractory and sensitive disease.…”

Section: Introductionmentioning

confidence: 99%

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Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

et al. 2020

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Background Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC. Methods In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months). Conclusions Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met. Clinical Trial registration Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

et al. 2020

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“…Efficacy in SCLC transformation patients was poorer than that in primary SCLC patients 15. It was reported that bevacizumab combined with chemotherapy was effective in SCLC in first-line treatment 16,17. In our case, we found apatinib was available in patients with SCLC transformation (Figure 5E).…”

Section: Discussionmentioning

confidence: 56%

<p>Third-Generation TKI Resistance Due to SCLC Transformation: A Case Report and Brief Review</p>

Chen¹,

He²,

Liu³

et al. 2019

OTT

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ObjectiveWe reported a case of pathologic type transformed from adenocarcinoma to small-cell lung cancer (SCLC) after being treated with third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).Materials and methodsThe lung cancer pathologic type was transformed from adenocarcinoma to SCLC after the treatment of third-generation EGFR-TKI for 4.3 months. Four times of lung biopsies were conducted at a different time and different lesions. And the patient was treated with a variety of regimens after SCLC transformation, including etoposide combined with carboplatin (EC), irinotecan combined with oxaliplatin (IO), Abraxane, and Apatinib. These treatments got a good response, but quick progression. We also monitored the dynamic change of serum neuron-specific enolase (NSE) and pro-gastrin releasing peptide (Pro-GRP).ResultsAdenocarcinoma could transform into SCLC after the treatment of TKI. Tumor cells were heterogeneity, so adenocarcinoma and SCLC could be co-existed. The fluctuation of the NSE was consistent with the response of treatment and the progression of the tumor.ConclusionRegimens for the primary SCLC were also available for the transformed SCLC, but the duration of the response was short. NSE could be an effective biomarker for dynamic monitoring of the efficacy in SCLC transformation.

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“…When used clinically, it causes severe side-effects such as leucopenia. thrombocytopenia, neutropenia and fatigue (4) and anorexia and constipation (5). Patients who received platinum treatment with a taxane were more likely to experience grade 2 to 4 neuropathy (6).…”

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confidence: 99%

Partial Protection of Paclitaxel-induced Neurotoxicity by Antioxidants

Hara

Sakagami

Shi

et al. 2018

In Vivo

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Abstract. Background Paclitaxel is an anticancer drug that inhibits calcium-induced depolymerization of tubulin and thus blocks the progression of mitosis (1). It is clinically applied for the treatment of ovarian, breast, stomach and non-small cell lung cancer (2, 3). When used clinically, it causes severe side-effects such as leucopenia. thrombocytopenia, neutropenia and fatigue (4) and anorexia and constipation (5). Patients who received platinum treatment with a taxane were more likely to experience grade 2 to 4 neuropathy (6). Paclitaxel has been reported to induce oxidative stress in liver (slight, but no significant decrease in glutathione in liver) (7). Considering many beneficial effects of antioxidants under optimal conditions (usually achieved by adopting lower doses that stimulate growth) (8, 9), prevention of chemotherapeutic drug-induced neurotoxicity by antioxidants has been actively studied in recent years (10,11).In order to search for substances that reduce neurotoxicity induced by paclitaxel, we first investigated whether nerve growth factor (NGF)-induced differentiating rat neuronal cells (used as neuron model) are also very sensitive to paclitaxel, like malignant cells. The possible protective activity of four antioxidants, docosahexaenoic acid (DHA), acetyl-L-carnitine hydrochloride (ALC), N-acetyl-L-cysteine (NAC) and sodium ascorbate, against neurotoxicity of paclitaxel was then investigated. 745

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Efficacy of nanoparticle albumin-bound paclitaxel regimens for relapsed small cell lung cancer

Cited by 17 publications

References 22 publications

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

<p>Third-Generation TKI Resistance Due to SCLC Transformation: A Case Report and Brief Review</p>

Partial Protection of Paclitaxel-induced Neurotoxicity by Antioxidants

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