Intratumoural chemotherapy of lung cancer for diagnosis and treatment of draining lymph node metastasis

Çelikoğlu, Firuz; Celikoğlu, S; Goldberg, Eugene P.

doi:10.1211/jpp.62.03.0001

Cited by 22 publications

(28 citation statements)

References 59 publications

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“…These criteria were chosen based on previous publications (Table 2). 16,47 Written informed consent was obtained from each patient before study enrollment. Patient characteristics upon admission are presented in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Hohenforst-Schmidt¹,

Zarogoulidis²,

Darwiche³

et al. 2013

DDDT

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Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.

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Section: Methodsmentioning

confidence: 99%

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Hohenforst-Schmidt¹,

Zarogoulidis²,

Darwiche³

et al. 2013

DDDT

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“…There has been a considerable amount of work done looking at intratumoral delivery of free anticancer drugs such as docetaxel (Yoo et al, 2010), cisplatin (Celikoglu et al, 2006a,b), and paclitaxel (Wang & Chen, 2012). Celikoglu group has produced some comprehensive reviews of the delivery of cytotoxic drugs by intratumoral injection, particularly via bronchoscopy and there appears to be a considerable opportunity to achieve even more in this treatment modality (Celikoglu et al, 2008(Celikoglu et al, , 2010. As discussed in these reviews, the mainstay of treatment for inoperable tumors in the lung has been external beam radiation; however, it is becoming increasingly obvious that this mode of treatment is insufficient as these patients continue to have and extremely poor prognosis.…”

Section: Intratumoral Injectionmentioning

confidence: 99%

Loco-regional administration of nanomedicines for the treatment of lung cancer

et al. 2015

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Lung cancer poses one of the most significant challenges to modern medicine, killing thousands every year. Current therapy involves surgical resection supplemented with chemotherapy and radiotherapy due to high rates of relapse. Shortcomings of currently available chemotherapy protocols include unacceptably high levels of systemic toxicity and low accumulation of drug at the tumor site. Loco-regional delivery of nanocarriers loaded with anticancer agents has the potential to significantly increase efficacy, while minimizing systemic toxicity to anticancer agents. Local drug administration at the tumor site using nanoparticulate drug delivery systems can reduce systemic toxicities observed with intravenously administered anticancer drugs. In addition, this approach presents an opportunity for sustained delivery of anticancer drug over an extended period of time. Herein, the progress in the development of locally administered nanomedicines for the treatment of lung cancer is reviewed. Administration by inhalation, intratumoral injection and means of direct in situ application are discussed, the benefits and drawbacks of each modality are explored.

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“…Although conventional chemotherapeutic agents are principally effective in killing cancer cells, one of their major limitations is the high dosage needed to achieve effective drug concentrations in the lung tissue when applied intravenously, which often results in unwanted dose-limiting side-effects. Chemotherapy agents currently administered for the treatment of lung cancer are predominantly administered by the injectable route [133][134][135]. However, recent research in targeted therapeutics for lung cancer involving inhalable systems [121] as pharmaceutical aerosols demonstrates this as an excellent mode of delivering drugs directly to the lungs for treating disease.…”

Section: Lung Cancer Treatment By Nebulized Delivery Of Nanocarriersmentioning

confidence: 99%

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Galvin

Thompson

Ryan

et al. 2011

Cell. Mol. Life Sci.

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Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.

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Intratumoural chemotherapy of lung cancer for diagnosis and treatment of draining lymph node metastasis

Cited by 22 publications

References 59 publications

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Loco-regional administration of nanomedicines for the treatment of lung cancer

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

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