Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas.

BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution. RESULTS: Sixteen patients (median age 13.5 years, range 3-19 years) received 53 cycles of gemcitabine/nab-paclitaxel. Twenty-nine cycles (55%) resulted in ≥Grade 3 toxicity, with nonhematologic Grade ≥3 toxicities occurring in only eight of 53 cycles (15%). Patients received red blood cell and platelet transfusions in 23% and 4% of cycles, respectively. Grade ≥3 infectious toxicities occurred in 4% of cycles. Of 14 patients with measurable disease, there were no complete responses (CR), one partial response (PR; 7%), and six patients (43%) with stable disease (SD; median SD: 4.5 months, range: 2-19 months). In total, 31% of the patients derived clinical benefit (CR + PR + SD ≥ 4 months). Median time to progression was 72 days with a 4-month progression-free survival of 31% ± 12% and 1-year overall survival of 19% ± 10%. With a median follow-up for all 16 patients of 21 months from the first treatment with gemcitabine/nab-paclitaxel, one (6%) remains alive with disease. CONCLUSIONS: Gemcitabine/nab-paclitaxel is a relatively safe regimen with mainly hematologic toxicities. It offers a well-tolerated, palliative option providing clinical benefit in a subset of patients. A phase I trial of this combination is underway.

Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement.

PURPOSE: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. METHODS AND MATERIALS: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. RESULTS: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse-free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse-free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. CONCLUSIONS: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.

Gemcitabine and docetaxel (GEMDOX) for the treatment of relapsed and refractory pediatric sarcomas.

BACKGROUND: Patients with relapsed pediatric sarcomas have a poor outcome and are in need of novel effective therapies. METHODS: We retrospectively reviewed the records of patients at Children's Healthcare of Atlanta who were treated with gemcitabine (675 mg/m(2)) intravenously (IV) on Day 1 and Day 8, and docetaxel (75 mg/m(2)) IV on Day 8, repeated every 3 weeks. RESULTS: Nineteen patients with a median age of 11 years were treated from 2006-2010 and received 123 total courses. Two patients (11%), both with rhabdomyosarcoma, demonstrated objectives responses [one complete response (CR) and one partial response (PR)]. Seven other patients (39%) had stable disease (SD). The 1-year progression-free survival (PFS) of the entire cohort was 24% ± 10% with a median time to progression of 2 months (range: 0.5-14 months). The 1-year overall survival (OS) was 43% ± 11%. Grade 3 or 4 toxicities occurred in 14 patients (74%) and 52 courses (42%), and were most commonly hematologic (neutropenia = 37, anemia = 17, and thrombocytopenia = 23 courses). CONCLUSIONS: The dismal outcomes for patients with relapsed and refractory sarcomas and the lack of effective sarcoma salvage regimens highlight the need for new approaches. This report of the therapeutic activity of gemcitabine and docetaxel (GEMDOX) in rhabdomyosarcoma and other pediatric reports describing activity in osteosarcoma and Ewing sarcoma suggest that this combination should be considered for formal evaluation in a pediatric specific clinical trial. At a minimum, it appears to offer a reasonable, tolerable, palliative option.

Intensity-modulated radiotherapy with use of cone-down boost for pediatric head-and-neck rhabdomyosarcoma.

PURPOSE: To report our initial experience using intensity-modulated radiotherapy (IMRT) with a cone-down boost for pediatric head-and-neck rhabdomyosarcoma (RMS). METHODS AND MATERIALS: A review of institutional treatment records identified children treated with IMRT for head-and-neck RMS between January 2000 and February 2007. All patients had undergone chemotherapy according to cooperative group RMS protocols. The initial planning target volume (PTV) covered the prechemotherapy tumor extent with variable margins, generally 1-2 cm. The boost PTV covered the postchemotherapy tumor volume, usually with a margin of 0.5-1 cm. RESULTS: A total of 20 patients were treated with IMRT for head-and-neck RMS. Of these 20 patients, 4 had Group II, 15 Group III, and 1 Group IV disease. The site was parameningeal in 12, nonparameningeal in 6, and orbit primary in 2. Of the 20 patients, 14 were treated with a cone-down boost after a median dose of 36 Gy (range, 30-45.6). The mean initial PTV was 213.5 cm(3), and the mean boost PTV was 76.9 cm(3). Patients received a median total dose of 50.4 Gy. The median follow-up time was 29 months. The 3-year Kaplan-Meier local control rate was 100%, although 1 patient developed an in-field recurrence 50 months after IMRT. The 3-year event-free survival rate, overall survival rate, and risk of central nervous system failure was 74%, 76%, and 7%, respectively. CONCLUSIONS: Our preliminary follow-up of pediatric head-and-neck RMS patients treated with IMRT revealed excellent local control. The initial targeting of the prechemotherapy tumor volume with 1-2-cm margin to 30.6 or 36 Gy followed by a cone-down boost to the postchemotherapy tumor volume with a 0.5-1-cm margin allowed for significant sparing of normal tissues and provided good local control.