motexafin-gadolinium and Adenocarcinoma

Motexafin gadolinium is a novel antineoplastic drug that disrupts cancer cell antioxidant systems, thus contributing to cellular death. In patients with lung cancer, motexafin gadolinium has been shown to increase the time to neurologic progression when given in combination with whole-brain radiotherapy in randomized phase III studies. Preclinical data suggest that this drug might also enhance the antineoplastic effects of chemotherapy.. In this one-arm, open label, phase I, dose-escalation study, we administered docetaxel (75 mg/m2), cisplatin (75 mg/m2), and motexafin gadolinium every 3 weeks to patients with metastatic non-small cell lung cancer. Twenty-one patients were treated at one of four motexafin dose levels.. The maximal tolerated motexafin dose was 10 mg/kg on day 1 of a 3-week cycle. Dose-limiting toxicities consisted of febrile neutropenia, hypertension, myocardial ischemia, and pneumonitis/pulmonary infiltrates. Other common grade 3-4 adverse events across all cohorts that did not appear to be exacerbated by motexafin gadolinium included granulocytopenia, fatigue, dehydration, nausea, and vomiting. Two episodes of myocardial ischemia and one sudden death of unknown cause were observed. Response rates were partial response (10%), stable disease (60%), and disease progression (30%).. The regimen studied was tolerable and showed activity in patients with metastatic non-small cell lung cancer. The recommended doses for future phase II trials are motexafin gadolinium 10 mg/kg, docetaxel 75 mg/m2, and cisplatin 75 mg/m2 intravenously on day 1 every 3 weeks. Caution is advised in patients with a history of cardiovascular disease.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Metalloporphyrins; Middle Aged; Prognosis; Survival Rate; Taxoids

Unresectable pancreatic cancer (UPC) has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT) as definitive treatment for UPC and the CA 19-9 response to therapy have an impact on overall survival (OS).. From 1997-2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy). All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other) and 24 received adjuvant chemotherapy.. 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy). Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19-9 post-CRT <90 U/mL was favorably associated with OS (12.3 versus 8.8 months, p = 0.012). Radiotherapy dose ≥54 Gy trended towards improved OS (11.3 versus 6.8 months, p = 0.089). By multivariable analysis, a delivered RT dose of ≥54 Gy (HR 0.47, p = 0.028) and minimum CA 19-9 post-CRT of <90 U/mL (HR 0.35, p = 0.008) were associated with OS.. CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19-9 <90 U/mL had improved likelihood of long-term survival.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; CA-19-9 Antigen; Capecitabine; Carcinoma; Chemoradiotherapy; Chemotherapy, Adjuvant; Deoxycytidine; Disease Progression; Dose-Response Relationship, Radiation; Female; Fluorouracil; Gemcitabine; Genetic Therapy; Genetic Vectors; Humans; Kaplan-Meier Estimate; Male; Metalloporphyrins; Middle Aged; Pancreatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Retrospective Studies; Treatment Outcome; Tumor Necrosis Factor-alpha

New photosensitizers proposed for photodynamic therapy (PDT) treatment of tumors need to be evaluated in animal models to determine the parameters needed for treatment. They also need to be compared with existing photosensitizers for efficacy. We examined the PDT response to lutetium-texaphyrin (PCI-0123) in a mouse mammary adenocarcinoma model and compared it with the PDT response seen when using Photofrin.. DBA/2 mice with SMT-F tumors were used to explore PCI-0123 toxicity, laser light dose, and drug dose effects on PDT response and to determine the most effective time for light application. The PDT response of PCI-0123-treated tumors was compared with that of Photofrin-treated tumors.. Treatment of tumors with 150 J/cm2 of 740 nm laser light 5-6 hr after PCI-0123 administration (40 mg/kg) resulted in a 100% response rate and a 55% cure rate. Tumors treated with 150 J/cm2 of 630 nm laser light 24 hr after Photofrin administration (10 mg/kg) resulted in a 67% response rate and a 16% cure rate.. PCI-0123 was found to be a more effective photosensitizer than Photofrin.

Topics: Adenocarcinoma; Animals; Dihematoporphyrin Ether; Female; Laser Therapy; Mammary Neoplasms, Animal; Metalloporphyrins; Mice; Mice, Inbred DBA; Photochemotherapy; Photosensitizing Agents; Tumor Cells, Cultured