Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303).

BACKGROUND: E2303 evaluated cetuximab, paclitaxel, and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) determining pathologic complete response (CR), event-free survival (EFS), and toxicity. PATIENTS AND METHODS: Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies (at week 8 in clinical complete responders and at week 14 if disease persisted). Chemoradiation (CRT) began week 9. If week 14 biopsy was negative, patients completed CRT (68-72 Gy); otherwise, resection was carried out. p16 protein expression status was correlated with response/survival. RESULTS: Seventy-four patients were enrolled; 63 were eligible. Forty-four (70%) were free of surgery to the primary site, progression, and death 1-year post-treatment. Following induction, 41 (23 CR) underwent week 8 primary site biopsy and 24 (59%) had no tumor (pathologic CR). Week 14 biopsy during chemoradiation (50 Gy) in 34 (15 previously positive biopsy; 19 no prior biopsy) was negative in 33. Thus 90% of eligible patients completed CRT. Overall survival and EFS were 78% and 55% at 3 years, respectively. Disease progression in 23 patients (37%) was local only in 10 (16%), regional in 5 (8%), local and regional in 2 (3%), and distant in 5 patients (8%). There were no treatment-related deaths. Toxicity was primarily hematologic or radiation-related. p16 AQUA score was not associated with response/survival. CONCLUSIONS: Induction cetuximab, paclitaxel, and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival. CLINICAL TRIALS NUMBER: NCT 00089297.

Development of herpes simplex virus-1 amplicon-based immunotherapy for chronic lymphocytic leukemia.

Herpes simplex virus (HSV)-based vectors have favorable biologic features for gene therapy of leukemia and lymphoma. These include high transduction efficiency, ability to infect postmitotic cells, and large packaging capacity. The usefulness of HSV amplicon vectors for the transduction of primary human B-cell chronic lymphocytic leukemia (CLL) was explored. Vectors were constructed encoding beta-galactosidase (LacZ), CD80 (B7.1), or CD154 (CD40L) and were packaged using either a standard helper virus (HSVlac, HSVB7.1, and HSVCD40L) or a helper virus-free method (hf-HSVlac, hf-HSVB7.1, and hf-HSVCD40L). Both helper-containing and helper-free vector stocks were studied for their ability to transduce CLL cells, up-regulate costimulatory molecules, stimulate allogeneic T-cell proliferation in a mixed lymphocyte tumor reaction, and generate autologous cytotoxic T lymphocytes (CTLs). Although helper-containing and helper-free amplicon stocks were equivalent in their ability to transduce CLL cells, a vigorous T-cell proliferative response was obtained using cells transduced with hf-HSVB7.1 but not with HSVB7.1. CLL cells transduced with either HSVCD40L or hf-HSVCD40L were compared for their ability to up-regulate resident B7.1 and to function as T-cell stimulators. Significantly enhanced B7.1 expression in response to CD40L was observed using hf-HSVCD40L but not with HSVCD40L. CLL cells transduced with hf-HSVCD40L were also more effective at stimulating T-cell proliferation than those transduced with HSVCD40L stocks and were successful in stimulating autologous CTL activity. It is concluded that HSV amplicons are efficient vectors for gene therapy of hematologic malignancies and that helper virus-free HSV amplicon preparations are better suited for immunotherapy.

Idiopathic thrombocytopenic purpura in Egyptian children.

350 patients with idiopathic thrombocytopenic purpura (ITP) aged 2/12-15 years (mean 6.3 +/- 2.7) were followed up during the period January 1st, 1975 to March 31, 1992. They constituted 40% of cases with hemorrhagic diathesis attending the Hematology/Oncology Clinic, Children's Hospital, Ain Shams University (relative frequency of 37.4/100.000 of the general Out-Patient Clinic in the same hospital). These patients presented with acute (71.4%), chronic (22.9%) and recurrent (5.7%) forms. The age of presentation was younger in acute ITP. In the recurrent form there was significant female predominance. Most cases of acute ITP (66%) presented in winter and spring, with a positive history of preceding viral illness in 50% in contrast to 10% in chronic form. Four chronic ITP cases developed lupus erythematosus; all were females > 9 years. As regards therapy, acute ITP cases with initial platelet count (PC) < 10 x 10(9)/l were randomized to receive either high-dose methyl prednisolone (HDMP) 10 mg/kg/day for 5 days i.v. (n = 10) or intravenous immunoglobulin (IVIG) 0.4 g/kg/day for 5 days (n = 10) or conventional-dose prednisone (CDP) 2 mg/kg/day 4 weeks p.o. (n = 10). A dramatic response was noticed in the first two groups. In chronic ITP, (n = 80) CDP induced complete response (CR) in 30% and partial response (PR) in 20%; 50% were nonresponders. Twenty-four refractory ITP with persistent PC < or = 20 x 10(9)/l received second-line therapy: vincristine 1.5 mg/m2/week i.v. 4 doses (n = 4) with no clinical or hematological improvement. IVIG 0.4 g/kg/day for 5 days (n = 8) with sustained CR only in 2 patients (25%) and PR in 2 patients (25%). Splenectomy was performed (n = 12) with CR in 50%; out of them, 2 patients had shown no improvement on prior IVIG therapy. In conclusion, ITP is a benign condition with no fatality reported, but it could run a chronic refractory course.

A field survey on child health in a rural community in Egypt.

A field survey in a village was carried out to study child health in a rural area. The vaccination scheme was found to be inadequate and the value of health education is stressed. Parasitic infestation was found to be higher than urban areas but significantly lower than 1959 and the latter is attributed to a safer water supply. Growth and development lagged behing the whole national standards particularly during the 1 - 6 years age period. Health care for the pre-school age, taking advantage of co-operation from medical faculties and local health authorities, is recommended.