Anthrapyrazoles and Interstitial Laser Phototherapy for Experimental Treatment of Squamous Cell Carcinoma

Abstract

Interstitial laser therapy (ILT) is an effective palliative treatment for advanced head and neck cancer, but recurrence often is seen at the margin. The objective of the current study was to test combined drug and laser therapy as an experimental approach for improved treatment of human squamous cell carcinoma (SCCA). Human SCCA tumor transplants were grown in nude mice and injected with the photosensitive anthrapyrazole CI-941 before ILT. Intralesional drug injections alone at levels ranging from 60 to 1200 microg/gm of tumor induced a growth delay at the higher doses, but recurrence was seen in all 35 tumors tested. SCCA tumor transplants injected with 240 microg/gm CI-941 followed after 4 hours by ILT with the KTP532 laser led to a complete response rate of 72% (21/29) compared with 45% (13/29) for ILT alone. Laser chemotherapy was a significant improvement compared with ILT when partial and complete responses were combined (P < 0.03). The results provide preclinical evidence that laser chemotherapy may become a useful minimally invasive treatment for advanced squamous cell carcinoma of the head and neck.

Laser Photo Chemotherapy: An Alternative Treatment for Cancer

“…This was the first effort in the literature to explore the concept of local injection of anti-cancer drug combined with laser interstitial therapy for cancer treatment. Additional testing in a larger group of animals in Germany by Graeber et al (1998) confirmed these results, which provide strong preclinical evidence in support of the hypothesis that photo chemotherapy may be an alternative treatment for human tumors. Similar LITT studies have followed with a translational experimental model combining intratumor cisplatin with Nd:YAG laser for thermal ablation of recurrent and advanced head and neck cancer (Paiva et al, 1998b;Graeber et al, 1999).…”

“…Ongoing clinical studies are being conducted to determine the impact that this alternative approach of combining laser and anti-cancer agents may have on the control of disease, survival and quality of life in cancer patients (Paiva et al, 2005b;Paiva et al, 2005c). In addition to the advantage of photo-activation, several of these light sensitive chemotherapeutic agents have been reported to exhibit enhanced toxicity in tumor cells after photo-thermal-activation (Chung et al, 2003;Graeber et al, 1999;Graeber et al, 1998;Paiva et al, 1995;Saxton et al, 1996). As a result, a potentially useful and less invasive approach for treatment of malignancies is to combine imaging guided interstitial laser surgery with conventional chemotherapy (Paiva et al, 2005b;Saxton et al, 1995).…”

Improved photochemotherapy of malignant cells with daunomycin and the KTP laser

“…KTP laser light also has been used surgically after coupling to a bare fiber in both the contact mode and noncontact mode with reported clinical effectiveness in controlling bleeding disorders as well as tongue and soft palate cancer resections in addition to laryngeal cancer treatment [21,22]. KTP laser fiberoptics recently were tested for interstitial treatment of transplanted human squamous-cell tumors after injection of the anthrapyrazole CI-941 [9,10]. This agent was selected as a more photosensitive and less toxic anthracycline-related drug than daunomycin for initial in vivo studies of human squamous-cell carcinoma transplants in nude mice [23,24].…”

“…This agent was selected as a more photosensitive and less toxic anthracycline-related drug than daunomycin for initial in vivo studies of human squamous-cell carcinoma transplants in nude mice [23,24]. The results showed a significantly improved cure rate of 72% after drug and laser therapy compared to 46% for laser treatment alone [10]. Delayed tumor regrowth and prolonged mean survival was seen after laser chemotherapy compared to either KTP laser alone or CI-941 injection alone.…”

“…Although interstitial laser therapy (ILT) is less invasive than surgical resection, it appears that ILT as a single treatment modality will fail in those cases in which tumors encroach upon heat-sensitive vital structures [7]. An alternative approach is to deliver laser photothermal emissions to tumors after uptake of light-and heat-sensitive anti-cancer drugs, allowing therapy at reduced thermal energy and elevated intratumor drug levels [8][9][10].…”