Dramatic response of teratoma-associated non--germ-cell cancer with all-trans retinoic acid in a patient with nonseminomatous germ cell tumor.

A patient with nonseminomatous germ cell cancer, treated with standard chemotherapy, subsequently developed a pathologically confirmed metastatic undifferentiated adenocarcinoma (non-germ-cell elements) arising from residual teratoma. Disease was present in both lobes of the liver and was deemed unresectable at the time of presentation. The patient was treated on a National Cancer Institute-sponsored institutional protocol with all-trans retinoic acid. After 60 days of oral therapy at a dose of 150 mg/m2/d (50 mg/m2 three times daily), the patient was found to have complete radiologic resolution of his hepatic metastases. He subsequently underwent surgery and his complete response was pathologically confirmed.

Oprelvekin: an alternative treatment for thrombocytopenia.

Oprelvekin (Neumega, Genetic Institute Co., Cambridge, MA) is a thrombopoietic growth factor approved by the U.S. Food and Drug Administration for the prevention of severe thrombocytopenia following myelosuppressive chemotherapy in patients with nonmyeloid malignancies. The most common side effects are edema, dyspnea, tachycardia, and conjunctival redness. Patient-care concerns include appropriate timing of administration, patient selection, dosing and administration issues, and the early identification and management of side effects.

A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy.

We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.

A phase II trial of subcutaneously administered recombinant human interleukin-2 in patients with relapsed/refractory thymoma.

The thymus is the site of T-cell maturation and contains T-cell precursors that differentiate into cytolytic T lymphocytes (CTLs) in vitro in the presence of interleukin-2 (IL-2). Malignant thymoma is often associated with a lymphocytic infiltration of these precursors. The antitumor effects of IL-2 are mediated in part by activated CTLs. Based on these considerations and anecdotal reports of its anti-tumor activity in thymoma, we conducted a Phase II trial of IL-2 in 14 patients with thymoma. IL-2 was administered s.c. at a dose of 12 x 10(6) IU/m2/day for 5 days for 4 weeks followed by a 2-week rest period. Patients were evaluated for response after each 6-week cycle, and those tolerating therapy with no disease progression were eligible for a maximum of 4 cycles. All patients had failed prior standard chemotherapy and 12 had received prior radiotherapy. All 14 patients were evaluable for toxicity and response. The median number of cycles received was two. One patient was removed from study during cycle 1 because of severe bronchospasm. Five patients required dose reductions for grade 3 toxicity (anorexia, nausea, hyperbilirubinemia, elevated SGPT, and skin desquamation, one patient each). Two patients developed new symptoms of myasthenia gravis while in the study and were removed (one for progressive disease, one for steroid requirement). There were no objective responses. The one patient who required steroids for newly diagnosed myasthenia gravis had a minor response. We conclude that subcutaneously administered IL-2, although it has acceptable toxicity, has no significant clinical activity in previously treated patients with advanced thymoma.