Table 2.
Selected microtubule-binding agents which have been approved or have undergone clinical evaluation
| Binding domain | Family | Agent | Approved Indications * | Clinical trials | Comments |
|---|---|---|---|---|---|
| Vinca | Vincas | Vincristine | ALL, lymphomas Various solid tumors |
Various tumor types | Natural compound Generic Parenteral administration |
| Vinblastine | Lymphomas Various solid tumors |
Various tumor types | Natural compound Generic Parenteral administration |
||
| Vinorelbine | Breast, NSCLC | Various tumor types | Semi-synthetic Generic Oral and parenteral administration |
||
| Vindesine | ALL, lymphoma Lung cancer | Various tumor types | Semi-synthetic Generic Parenteral administration |
||
| Vinflunine (Javlor®, Pierre Fabre) | Bladder | Breast in combination with Herceptin | Semi-synthetic Parenteral administration |
||
| Liposomal vincristine | - | leukemia melanoma, myeloma, sarcoma | Prolonged and regular delivery | ||
| Dolastatins | soblidotin (TZT-1027) | - | Phase I in advanced solid tumors No ongoing trials |
Responses in NSCLC and esophageal cancer | |
| romidepsin Istodax® Gloucester Pharmaceuticals |
Cutaneous T cell lymphoma | Myeloma, lymphoma, solid tumors | Dolastatin 15 analog | ||
| brentuximab vedotin (SGN 35) | - | Phase III trial recruiting in Hodgkin’s disease | Antibody-vectorized agent directed against CD30 positive malignancies | ||
| Cryptophycins | Cryptophycin 52 LY355703 | - | Phase II NSCLC Terminated | Caused significant neurological toxicity | |
| Halichondrin | Eribulin (E7389, NSC 707389) | - | Phase III in advanced breast cancer | Improved OS when compared to treatment of physician’s choice | |
| Hemiasterlin | E-7974 | - | Phase I | Hematological MTD | |
| Maytansinoids | Mertansine immunoconjugates (BT-062, IMGN388, BIIB015) | - | Head and neck, oesophagus, advance HER2 positive breast cancer, myeloma | Phase II and III underway | |
| Folate vectorized vinca alkaloid | EC-145 | Ovarian, endometrial, lung cancer | Folate-targeted vinca alkaloid conjugate | ||
| Taxane | Taxanes | Paclitaxel Taxol® |
Ovarian, breast, NSCLC | Various solid tumor types | May induce hypersensitivity reactions |
| Docetaxel Taxotere® |
Breast, NSCLC, prostate, stomach, head and neck | Various solid tumor types | May induce hypersensitivity reactions | ||
| cabazitaxel (XRP6258) Jevtana® |
Metastatic hormone-resistant prostate | Approved June 2010 | |||
| Milataxel (MAC-321, TL-139) | - | Phase II mesothelioma | Active in preclinical models of resistance to taxanes 203,204 | ||
| Larotaxel (XRP9881) | - | Phase III pancreatic | Active in preclinical models of resistance to taxanes, poor MDR substrate 205–207. | ||
| Ortataxel IDN-5109 BAY 59-8862 |
- | Phase II taxane-resistant tumors | Active in Pgp-expressing models 208 | ||
| Tesetaxel | - | Phase II gastric | Oral administration | ||
| DJ-927 | Phase II colorectal Phase II melanoma |
Is not transported by Pgp209,210 | |||
| BMS 275183 | - | Phase II NSCLC Terminated | Oral administration Unpredictable pharmacokinetics |
||
| TPI 287 (ARC-100) | - | Phase II prostate cancer Phase I pediatric CNS cancers |
Investigated in neurological tumors in combination with temozolomide | ||
| Nab-paclitaxel (ABI-007) Abraxane® Abraxis Bioscience Nab-docetaxel (ABI-008) |
Breast cancer | Various solid tumors Prostate cancer |
Shorter infusion times than paclitaxel Does not require premedication |
||
| NKTR-105 | Phase I | PEGylated formulation of docetaxel; pre-treatment with corticosteroids not required | |||
| Epothilones | Ixabepilone Ixempra® Bristol Myers Squibb |
Breast cancer | Solid tumors | Several ongoing trials in solid tumors Is not a substrate for Pgp |
|
| Patupilone (epothilone B) | - | Brain metastases in breast cancer, ovarian, melanoma, other solid tumors | Penetrates in the CNS Is not a substrate for Pgp Possesses radiosensitizing properties | ||
| Sagopilone | - | Glioblastoma, prostate, lung cancers | First fully synthetic epothilone Penetrates in the CNS | ||
| KOS 1584 (epothilone D) | - | NSCLC Phase II | Investigated in breast and prostate cancer | ||
| Discodermolide | - | - | Phase I Terminated | Pulmonary toxicity | |
| Colchicine | CI-980 | - | - | Phase II trials Terminated | No responses observed in sarcoma or colorectal cancer211,212 |
| 2 methoxy-estradiol (ME2) Panzem® EntreMed |
- | - | Phase II in prostate, myeloma, glioblastoma | Endogenous metabolite of estradiol with no affinity for estrogen receptor Side effects: DVT and increased transaminases |
|
| 1069C85 | - | - | Phase I Terminated | Oral administration 213 | |
| ABT 751 E7010 |
- | - | Phase II in various solid tumors No ongoing trials |
Orally bioavailable sulfonamide Neurotoxicity 214 |
|
| Indibulin | - | - | Phase I/II in metastatic breast cancer | Discriminates between neuronal and non-neuronal tubulin 148,215 | |
| Combretastatins | Fosbretabulin (CA4 phosphate) | - | Phase II in lung and thyroid cancer, glioma | Vascular disrupting agent | |
| Verubulin | Phase II glioblastoma | Vascular disrupting agent | |||
| Crinobulin | - | Phase I | Vascular disrupting agent | ||
| Plinabulin | Phase I | Vascular disrupting agent | |||
| Ombrabulin | - | Phase III in sarcoma | Vascular disrupting agent | ||
| Other | Noscapinoids | Noscapine | - | Phase II multiple myeloma | Oral opium alkaloid used as antitussive |
| Estramustine | - | Prostate cancer | Combination with taxanes, vincas, ixabepilone in prostate cancer | Generic Binds to microtubule associated protein |
ALL: acute lymphoblastic leukemia; CNS: central nervous system; DVT: deep vein thrombosis; MTD: maximal tolerated dose; NSCLC: non small cell lung cancer; OS: overall survival; Pgp: P glycoprotein
Data in this table have been obtained from clinicaltrials.gov, Pubmed, ASCO, company sites and the Thomson Pharma Partnering database.