MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Bez efektu

Iodine-131 MIBG scintigraphy in small cell lung cancer

  • 131I-MIBG, which is recognized and taken up by the APUD system to monitor disease activity in patients with small cell carcinoma of the lung.
  • Unable to detect reproducible correlations between the images produced by conventional radiographic techniques and the images produced by our radiopharmaceutical.
    • Will probably not be useful for localization of metastatic small cell lung carcinoma.
  • https://einstein.elsevierpure.com/en/publications/iodine-131-mibg-scintigraphy-in-small-cell-lung-cancer
  • Asi se to nevychytalo všude
    • Některé nádorove bunky asi nevychytaly jak měly a nebo byly již rozlezlé ve více místech než se prve zobrazilo na CT
  • Možná obojí - korelace k zobrazování a detekci nebyla



PLK1 inhibitors


Verapamil

  • Proliferation of drug resistant tumour following chemotherapy is the principal cause of treatment failure in small cell lung cancer (SCLC)
  • Verapamil
    • Partially restore drug sensitivity in tumour cells rendered resistant in vitro

Two hundred and twenty-six patients

  • Four cycles of cyclophosphamide (750 mg m-2), doxorubicin (40 mg m-2) and vincristine (1.4 mg m-2) on Day 1
  • And etoposide (75 mg m-2) on Days 1, 2 and 3, repeated at 21 day intervals.
  • Randomised to the verapamil arm
    • Oral verapamil 120 mg qid for 5 days with each course of chemotherapy
  • Over 75% of patients completing all four cycles
  • no significant differences in general toxicities between the two arms
    • More severe alopecia in the verapamil treatment group (P = 0.045)
  • No statistically significant differences in response or survival
  • pubmed.ncbi.nlm.nih.gov/8398713/


Epidermal growth factor receptor (EGFR) antagonists

Erlotinib and gefitinib

  • Effective in NSCLC
  • SCLC either do not express the EGFR or express very small amounts
  • Clinical trials have not shown any benefit of treatment with EGFR inhibitors in SCLC 95.
  • erj.ersjournals.com/content/35/1/202

Vandetanib

  • Orally bioavailable inhibitor of VEGF receptor 2
    • VEGFR-2 or kinase insert domain receptor (KDR)
      • To a lesser extent, EGFR

Phase II trial

  • 107 patients who exhibited a partial or complete response to their induction therapy were randomly assigned to vandetanib or placebo
  • Vandetanib failed to demonstrate efficacy as maintenance therapy for SCLC.
  • erj.ersjournals.com/content/35/1/202

Thalidomide

  • Antiangiogenic agent
  • Promising results as first-line chemotherapy and as maintenance therapy in phase II trials

2 large randomised phase III trials failed to show a significant benefit of thalidomide in the treatment of SCLC

Temsirolimus

  • An inhibitor of the mammalian target of rapamycin

Maintenance therapy in ES-SCLC in a phase II Eastern Cooperative Oncology Group trial.

  • Stable or responding disease following induction chemotherapy were treated with temsirolimus
  • Seemed not to increase progression-free survival in this patient population
  • erj.ersjournals.com/content/35/1/202

Imatinib

  • Stem cell factor coexpressed with its tyrosine kinase receptor (c-kit) on SCLC tumoural cells
  • Imatinib, a small-molecule inhibitor of several receptor tyrosine kinases, including c-kit,
    • Inhibited tumoural cell growth - promising in vitro results

Phase II trials

Matrix metalloproteinases (MMPs) inhibitors

  • MMPs - proteolytic enzymes
    • Released by stromal and tumoural cells
    • Degrade the extracellular matrix, and thus permit the migration of tumoural cells through the extracellular matrix
    • Leading to their dissemination and the development of metastatic disease
  • Increased expression of metalloproteinases = poor prognosis in SCLC

Clinical trials with two different MMP inhibitors (marimastat and BAY 12-9566)

Vaccine therapy

  • SCLC cells express several antigens from ganglioside family
    • Polysialic acid,
    • Fucosyl GM1, GM2, GD2 and GD3
  • Not expressed on normal tissue
  • Targets for vaccine therapy

Phase III trials in SCLC with vaccine therapy targeted against these gangliosides

Antisense oligonucleotides

  • Target specific RNA sequences of genes involved in tumoural cell growth.

Oligonucleotide that targets Bcl-2

  • An inhibitor of apoptotic cell death highly expressed in SCLC
  • In vitro studies induce apoptosis and enhance the cytotoxicity of chemotherapeutic agents in SCLC cell lines

A multicentric randomised phase II trial

  • Found no evidence of improvement in response rate or overall survival when oblimersen was combined with carboplatin plus etoposide
    • Compared to chemotherapy alone
  • Proportion of patients alive at 1 yr was 24% with oblimersen and 47% without oblimersen
    • Suggesting a worse outcome for patients receiving this drug.
  • erj.ersjournals.com/content/35/1/202

Verapamil

A randomised clinical study of verapamil in addition to combination chemotherapy in small cell lung cancer

  • No statistically significant differences in response (P = 0.582) or survival (P = 0.290) data were seen.
  • Absence of a significant improvement in response or survival using verapamil
    • May relate to the low blood levels of verapamil seen in the clinic (0.8 microM),
    • In contrast to those known to be maximally active in vitro (> 6 microM)
    • Or to the presence of other cellular mechanisms by which drug resistance develops.
  • www.nature.com/articles/bjc1993433


O úroveň výše

Poslední aktualizace: 10. 12. 2023 2:01:09