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Pegylated liposomal doxorubicin has activity in both breast and ovarian cancer. Preclinical data noted that ZD1839 acts synergistically with chemotherapy. Given the lack of cross-resistance between these two agents, a phase I trial was initiated examining the safety and efficacy of the combination of liposomal doxorubicin and ZD1839 in patients with recurrent gynecologic or metastatic breast cancer. Dose-limiting toxicity (DLT) was defined within the first two cycles of treatment. Escalating doses of liposomal doxorubicin were administered every 4 weeks with ZD1839. Pharmacokinetic analysis and correlative studies were performed. Thirty-five patients were enrolled in this study: six in each cohort. One DLT (febrile neutropenia) was observed in cohort 2. Dose level 3 was determined to be the maximum tolerated dose (MTD), and an additional ten patients were accrued. Serious adverse events (SAEs) included one patient with mental status changes believed secondary to disease progression and two central nervous system (CNS) bleeds believed to be unrelated to the combination of study agents. Toxicities were generally mild except for skin and gastrointestinal toxicity. No cardiac toxicity was observed. The best response to therapy included four partial responses and 20 patients with stable disease. Liposomal doxorubicin with ZD1839 is an active regimen but is associated with increased skin toxicity in patients with advanced breast and gynecologic cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety and feasibility of concurrent radiation therapy and paclitaxel-based adjuvant chemotherapy, given either weekly or every 3 weeks, after adjuvant doxorubicin and cyclophosphamide (AC). Methods and Materials: After definitive breast surgery and AC chemotherapy, 40 patients with operable Stage II or III breast cancer received protocol-based treatment with concurrent paclitaxel and radiation therapy. Paclitaxel was evaluated on 2 schedules, with treatment given either weekly × 12 weeks (60 mg/m2), or every 3 weeks × 4 cycles (135–175 mg/m2). Radiation fields and schedules were determined by the patient’s surgery and pathology. The tolerability of concurrent therapy was evaluated in cohorts of 8 patients as a phase I study. Results: Weekly paclitaxel treatment at 60 mg/m2 per week with concurrent radiation led to dose-limiting toxicity in 4 of 16 patients (25%), including 3 who developed pneumonitis (either Grade 2 [1 patient] or Grade 3 [2 patients]) requiring steroids. Efforts to eliminate this toxicity in combination with weekly paclitaxel through treatment scheduling and CT-based radiotherapy simulation were not successful. By contrast, dose-limiting toxicity was not encountered among patients receiving concurrent radiation with paclitaxel given every 3 weeks at 135–175 mg/m2. However, Grade 2 radiation pneumonitis not requiring steroid therapy was seen in 2 of 24 patients (8%) treated in such a fashion. Excessive radiation dermatitis was not observed with either paclitaxel schedule. Conclusions: Concurrent treatment with weekly paclitaxel and radiation therapy is not feasible after adjuvant AC chemotherapy for early-stage breast cancer. Concurrent treatment using a less frequent paclitaxel dosing schedule may be possible, but caution is warranted in light of the apparent possibility of pulmonary injury. [Copyright &y& Elsevier]