Phase I/II Study of Amrubicin and Nedaplatin in Patients with Untreated, Advanced, Non-Small Cell Lung Cancer

Ogawara, Daiki; Nakamura, Yoichi; Fukuda, Minoru; Nakatomi, Katsumi; Yamaguchi, Hiroyuki; Motoshima, Kohei; Mizoguchi, Kosuke; Nakano, Hirofumi; Takemoto, Shinnosuke; Gyotoku, Hiroshi; Nagashima, Seiji; Kohno, Shigeru

doi:10.1159/000371870

Cited by 3 publications

(3 citation statements)

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“…It is widely used as the first-line treatment for non-small cell lung cancer, cervical cancer, ovarian cancer, nasopharyngeal cancer, esophageal cancer, and other common malignancies. [4][5][6] Compared with first-generation platinum-based cisplatin, nedaplatin causes a significantly lower incidence of adverse reactions, such as hematologic toxicity, nephrotoxicity, and gastrointestinal symptoms, and does not require hydration at the time of use. [7,8] HSR to nedaplatin is an IgE-mediated tachyphylaxis type I reaction, [9] in which the patient body is already in a sensitized state after a first exposure to the allergen, and the HSR occurs upon re-exposure.…”

Section: Discussionmentioning

confidence: 99%

Hypersensitivity reaction to nedaplatin: A case report and literature review

Gan,

2023

Medicine

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Rationale: Although rare, systemic hypersensitivity reactions to nedaplatin chemotherapy arise rapidly and can be life-threatening. The causes are unclear, and multiple potential mechanisms exist. Here, we report a case of systemic hypersensitivity reaction to nedaplatin and review the literature to establish a recommended protocol. Patient concerns: A 62-year-old man was being treated for squamous lung cancer with multiple metastases. On the first day of chemotherapy, 5 minutes after nedaplatin infusion, he developed panic, shortness of breath, and dyspnea with rapid heart rate, reduced oxygen saturation, and elevated blood pressure. Diagnoses: The symptoms indicated that the patient had developed a severe hypersensitivity reaction to nedaplatin, which could be life-threatening without immediate intervention. Intervention: Nedaplatin was discontinued, and he was treated with oxygen, ECG monitoring, finger pulse oximeter monitoring, 10 mg dexamethasone sodium phosphate injected intravenously, 20 mg diphenhydramine hydrochloride injected intramuscularly, and 40 mg methylprednisolone sodium succinate injected intravenously. Outcome: His allergic symptoms resolved, and once his vital signs stabilized, he was given 5 mg oral desloratadine once daily and 10 mg oral ebastine once daily to alleviate the effects of the allergic reaction. Once his vital signs remained stable without any special supportive treatment, he was discharged from the hospital. His chemotherapy regimen was discontinued, with no plan for a follow-up treatment due to the possibility of cross-allergic reactions between platinum-based drugs. Lessons: Clinical use of nedaplatin should be monitored and managed intensively for prevention and treatment of hypersensitivity reactions. Care should be taken to control the titration rate during infusion while closely monitoring vital signs. Clinical staff should be prepared to treat allergic symptoms as soon as they appear. The acute phase should involve immediate discontinuation of the drug; intravenous saline infusion for volume expansion; rapid assessment of circulation, airway, respiration, state of consciousness, and skin condition; and administration of oxygen, antihistamines, and epinephrine as appropriate for anaphylaxis. More randomized clinical trials are needed to elucidate appropriate preventative and management strategies to improve patient safety and support their successful completion of clinical treatment programs.

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Section: Discussionmentioning

confidence: 99%

Hypersensitivity reaction to nedaplatin: A case report and literature review

Gan,

2023

Medicine

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“…A phase II clinical study in Japan showed that NDP is very effective in the treatment of small cell lung cancer and non-small cell lung cancer [11]. More importantly, it was reported that only incomplete cross-resistance with cisplatin and carboplatin was observed in patients [18,19].…”

Section: Discussionmentioning

confidence: 99%

Nedaplatin reduces multidrug resistance of non-small cell lung cancer by downregulating the expression of long non-coding RNA MVIH

et al. 2020

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Cisplatin-based chemotherapy is the standard treatment for non-small cell lung cancer (NSCLC). However, drug resistance emergences after treatment. Long non-coding RNA microvascular invasion in hepatic cancer (MVIH) plays an important role in drug resistance in a variety of cancers. This study investigates the role of nedaplatin on multidrug resistance in NSCLC and its relationship with MVIH. Lung cancer A549 and H1650 cells were treated with cisplatin to obtain multidrug-resistant A549/DDP and H1650/ DDP cells. A549/DDP and H1650/ DDP cells were treated with nedaplatin, MVIH siRNA and siRNA NC. It was found that both MVIH siRNA and nedaplatin significantly reduce the mRNA expression of MVIH in A549/DDP and H1650/ DDP cells. MTT assay showed that the proliferation of MDR cells was significantly higher than that of other cells. Nedaplatin and MVIH siRNA significantly inhibit the proliferation of A549 and H1650 cells. The results of colony formation assay were consistence with MTT results. Nedaplatin and MVIH siRNA significantly reduced colony formation in MDR cells. Flow cytometry showed that NDP and MVIH siRNA significantly decrease the proportion of cells in G0/G1 and increase the proportion of cells in S phase compared with untreated and MDR cells. The apoptotic rate of MDR cells was significantly lower than that of other cells, while the apoptosis rate of cells in NDP and MVIH siRNA group was significantly higher than that of the other three groups of cells. Wound healing assay and Transwell chamber experiments confirmed that both NDP and MVIH siRNA significantly reduced the migration and invasion abilities of MDR cells. The expression of E-cadherin in MDR cells was significantly lower than that in untreated cells, and the expression of N-cad, α-SMA and Vimentin significantly increased in the MDR cells. NPD and MVIH siRNA reverse the EMT process. In conclusion, LncRNA MVIH is upregulated in drug resistant NSCLC cells. Nedaplatin can reduce the expression of MVIH and reverse EMT process, thus reversing the drug resistance of cisplatin in non-small cell lung cancer cells.

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“…A randomized phase III study involving SCC patients showed that overall survival was longer with a combination of nedaplatin and docetaxel than with a combination of cisplatin and docetaxel . Amrubicin is a novel DNA topoisomerase II inhibitor; our previous phase I/II study revealed that a chemotherapeutic combination of amrubicin and nedaplatin was well tolerated, and that the overall response rate (ORR) was 48.6% (17 of 35 cases) for advanced non‐small cell lung cancer . The subset analysis (unpublished data) also suggested that the combination of nedaplatin and amrubicin was more effective in treating SCC (ORR, 70.0%; 7 of 10 cases) compared to non‐SCC (ORR, 40.0%; 10 of 25 cases).…”

Section: Introductionmentioning

confidence: 97%

Phase II study of nedaplatin and amrubicin as first‐line treatment for advanced squamous cell lung cancer

et al. 2019

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Background The first‐line treatment for squamous cell lung cancer (SCC) has not necessarily been established; however, our previous exploratory study suggested that the combination of nedaplatin and amrubicin would be a promising treatment approach for patients with SCC. Therefore, a phase II study of this chemotherapeutic combination was designed to evaluate its efficacy and safety for treatment‐naïve patients with advanced SCC. Methods A total of 21 treatment‐naïve patients with stage IIIB/IV or postoperative recurrent SCC were enrolled from six institutions. Nedaplatin (100 mg/m2) on day 1 and amrubicin (25 mg/m2) on days 1–3 were administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR), while the secondary endpoints included overall survival (OS), progression‐free survival (PFS), and drug toxicities. Results Partial response was observed in seven of 21 cases (ORR, 33.3%; 95% confidence interval [CI], 14.5–52.2). Disease control rate, which includes stable disease, was 71.4%. Median OS and PFS was 14.6 and 4.1 months, respectively. This regimen did not cause any treatment‐related deaths. Grade 3/4 neutropenia developed in 8 of 21 cases (38.1%); however, febrile neutropenia developed in only 9.5% of the cases. Grade 3/4 gastrointestinal or neuromuscular toxicities were not observed. Conclusion The efficacy of the combination of nedaplatin and amrubicin was comparable to that of other conventional chemotherapeutic regimens for treatment‐naïve patients with advanced SCC, and no severe gastrointestinal or neuromuscular toxicities were observed. This combination therapy may be an alternative treatment approach, particularly in patients who cannot tolerate gastrointestinal or neuromuscular toxicities.

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Phase I/II Study of Amrubicin and Nedaplatin in Patients with Untreated, Advanced, Non-Small Cell Lung Cancer

Cited by 3 publications

References 20 publications

Hypersensitivity reaction to nedaplatin: A case report and literature review

Hypersensitivity reaction to nedaplatin: A case report and literature review

Nedaplatin reduces multidrug resistance of non-small cell lung cancer by downregulating the expression of long non-coding RNA MVIH

Phase II study of nedaplatin and amrubicin as first‐line treatment for advanced squamous cell lung cancer

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