Intratumoral administration of cisplatin through a bronchoscope followed by irradiation for treatment of inoperable non-small cell obstructive lung cancer.

PURPOSE: Patients presenting with inoperable non-small cell carcinoma of the lung associated with severe bronchial obstruction are at a high risk for developing post-obstructive pneumonia or respiratory failure. This often leads to death in weeks to months. Several studies suggest that initial use of debulking of obstructed airways by Nd-YAG laser photo resection or by cryotherapy lessens morbidity by reducing infections and respiratory insufficiencies. This can shorten hospitalization, improve the quality of life, and prolong survival. It has also been demonstrated that patients first treated for debulking and then by irradiation have better survival than similar patients treated with irradiation alone. Intratumoral (IT) injection of cytotoxic drugs (IT chemotherapy) has also been successfully used to debulk airways. The aim of the present work was to study the effectiveness, safety, and feasibility of initial debulking by IT chemotherapy with cisplatin combined with irradiation with a curative intent in the treatment of obstructive inoperable non-small cell lung cancer. PATIENTS AND METHODS: Twenty three patients were treated first by bronchoscopic IT injection of up to 40 mg cisplatin solution (4 mg/ml), administered weekly four times (on days: 1, 8, 15, 22) and then by irradiation. RESULTS: At the end of a 3-week period of IT treatment, 11 of 23 patients showed an increase in airway lumen diameter of more than 50% (good response), 8 patients showed an improvement of 25-50% (partial response) and 4 patients showed an increase of less than 25% (small response). Overall, debulking by IT chemotherapy was considered clinically effective in 19 of 23 patients and only marginally effective in 4 patients. Statistical analysis indicated a statistically significant improvement in lumen diameter (P < 0.001) for all patients. The combination of IT chemotherapy and irradiation resulted in prolonged survival in the patients with good response (median survival 636 days) compared to patients with partial response (median survival 342 days). The four patients with only a small response had a median survival of 202 days. CONCLUSIONS: Debulking by intratumoral injection of cisplatin was shown to be a safe, simple, and cost effective procedure. There were no severe side effects and complications. Initial debulking of obstructed airways by IT administration of cisplatin, followed by irradiation requires further studies in order to determine its effect on survival.

Efficacy of mitoxantrone-loaded albumin microspheres for intratumoral chemotherapy of breast cancer.

Systemic toxicity of intravenously delivered chemotherapy is a limiting factor in the treatment of many cancers. We have shown that intratumoral injection of antineoplastic drugs can provide high localized drug concentrations with greatly reduced systemic toxicity. Using albumin microspheres as a drug carrier, localized and sustained release of chemotherapeutic drugs has been achieved by intratumoral injection, thus increasing the intratumoral dose and antitumor efficacy. Microspheres provide the advantages of localized, prolonged drug release. The efficacy and toxicity of intratumoral free mitoxantrone or mitoxantrone-loaded albumin microspheres were evaluated in a murine breast cancer model. In the same model, a combination of these two therapies was also evaluated. Results indicated that intratumoral mitoxantrone, especially in microsphere preparations, significantly improved survival and decreased systemic toxicity.