Therapy Detail
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| Therapy Name | Crizotinib + Cyclophosphamide + Topotecan |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Crizotinib | Xalkori | PF-02341066 | ALK Inhibitor 32 BCR-ABL Inhibitor 32 MET Inhibitor 59 RON Inhibitor 11 ROS1 Inhibitor 20 | Xalkori (crizotinib) inhibits ALK kinase, ALK fusion proteins, c-Met, ROS1 fusion proteins, and MST1R (RON), resulting in growth inhibition of tumor cells (PMID: 26951079, PMID: 22617245). Xalkori (crizotinib) is FDA approved for use in patients with ALK- or ROS1-positive (rearrangements and fusions) metastatic non-small cell lung cancer, in pediatric patients 1 year and older and young adults with relapsed or refractory, ALK-positive systemic anaplastic large cell lymphoma, and in adult and pediatric patients 1 year and older with ALK-positive, unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (FDA.gov). |
| Cyclophosphamide | Cytoxan | CPM | Chemotherapy - Alkylating 18 | Cytoxan (cyclophosphamide) is an alkylating agent, which inhibits DNA replication (NCI Drug Dictionary). Cytoxan (cyclophosphamide) is FDA approved in multiple hematological malignancies, breast cancer, neuroblastoma, ovarian cancer, and retinoblastoma (NCI Drug Dictionary). |
| Topotecan | Hycamtin | Topotecan Hcl | Topotecan binds to topoisomerase I and stablizes complexes with DNA, resulting in decreased repair of DNA single-strand breaks, and potentially leading to cell death (NCI Drug Dictionary). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ALK F1174L TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in xenograft models of a crizotinib-resistant human neuroblastoma cell line harboring ALK F1174L and wild-type TP53 (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 P177T | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 P177T in culture (PMID: 26438783). | 26438783 |
| ALK F1174L | neuroblastoma | conflicting | Crizotinib + Cyclophosphamide + Topotecan | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan resulted in progressive disease within 1 cycle of therapy in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1174L and PIK3CA C692Ffs*8 (PMID: 34210658). | 34210658 |
| ALK F1174L | neuroblastoma | conflicting | Crizotinib + Cyclophosphamide + Topotecan | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan resulted in a complete response after 2 cycles in a one pediatric patient, and a clinical response with stable disease lasting 7 months in another pediatric patient with relapsed neuroblastoma harboring ALK F1174L (PMID: 36765519). | 36765519 |
| ALK wild-type TP53 mut | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 wild-type | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and wild-type TP53 in culture (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 H168R | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) did not improve the effect of Topotecan and Cytoxan (cyclophosphamide) on tumor growth suppression in xenograft models of a human neuroblastoma cell line harboring wild-type ALK and TP53 H168R (PMID: 26438783). | 26438783 |
| ALK F1245C TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Pdx | Actionable | In a preclinical study, Xalkori (crizotinib) worked synergistically with Topotecan and Cytoxan (cyclophosphamide), resulting in sustained tumor regression in crizotinib-resistant neuroblastoma PDX models harboring ALK F1245C and wild-type Tp53 (PMID: 26438783). | 26438783 |
| ALK R1275Q | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to sustain tumor regression in human neuroblastoma cell line xenograft models harboring ALK R1275Q and wild-type TP53 (PMID: 26438783). | 26438783 |
| ALK mut TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in patient-derived neuroblastoma cell lines harboring Alk mutations and functional TP53, resulting in growth inhibition in culture and tumor regression in animal models (PMID: 26438783). | 26438783 |
| ALK amp TP53 wild-type | neuroblastoma | sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) demonstrated synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) in neuroblastoma cell lines harboring Alk amplification and functional TP53, resulting in growth inhibition in culture (PMID: 26438783). | 26438783 |
| ALK wild-type TP53 C176F | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 C176F in culture (PMID: 26438783). | 26438783 |
| ALK act mut TP53 wild-type | neuroblastoma | predicted - sensitive | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Xalkori (crizotinib), Topotecan, and Cytoxan (cyclophosphamide) synergized to delay tumor growth in xenograft models of a human neuroblastoma cell line harboring constitutively phosphorylated wild-type Alk and wild-type TP53 (PMID: 26438783). | 26438783 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|
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