Lymph node metastasis of soft tissue tumors: a cytomorphologic study.

OBJECTIVE: To study the frequency of regional lymph node metastasis of soft tissue tumors (STT) and to evaluate the utility of fine needle aspiration cytology (FNAC) as an initial investigative modality. STUDY DESIGN: A prospective and retrospective study of over 6 years (1998-2004) was performed to look for frequency of STT metastasizing to lymph nodes. FNAC of enlarged nodes was performed as a routine outpatient procedure after obtaining complete clinical details. Histopathology and immunohistochemistry were correlated where available. RESULTS: Lymph node enlargement was seen in 23 of 241 patients with STTs, of which 19 cases showed involvement (7.88%), synchronous with primary in 12 cases and metachronous in 7 cases. The most common sites of primary tumor were the lower extremity and head and neck region with involved regional lymph nodes. STTs commonly involving lymph nodes were rhabdomyosarcoma and extraskeletal Ewing's/primitive neuroectodermal tumor (PNET); other rare tumors included malignant granular cell tumor, epithelioid hemangioendothelioma, mediastinal ganglioneuroblastoma, angiosarcoma and epithelioid sarcoma. CONCLUSION: Lymph node aspirates should be examined for alien cells, particularly smears that are paucicellular and demonstrate cystic change. Lymph node metastasis of STT is rare and influences staging, treatment and prognosis. Enlarged regional nodes should be examined with FNAC.

Safety, tolerability, and pharmacokinetics of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory cancer patients in a bridging phase I study.

The purpose of this bridging phase I study was to characterize the toxicity, pharmacokinetics, and antitumor effects of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given daily for 5 consecutive days for 2 weeks, repeated every 3 weeks at 81 mg/m(2). Adverse events were monitored following NCI-CTC. Blood samples were processed for bioanalysis using a validated high-performance liquid chromatography method. The pharmacokinetics of lactone and total (lactone + carboxylate) forms was determined on days 1 and 12 using a noncompartmental pharmacokinetic method. Pharmacokinetic data with the capsule formulation were compared with previously reported pharmacokinetic parameters with a suspension formulation. Efficacy was evaluated by applying World Health Organization criteria. Six patients received 10 courses of therapy. Thrombocytopenia and diarrhea were dose-limiting toxicities. The upper limit of the area under the curve of DRF-1042 (lactone and total) with the capsule formulation was higher than a suspension formulation at a similar dose on day 1 (lactone: capsule = 8.53 microMxh, suspension = 5.33 microMxh; total: capsule = 393 microMxh, suspension = 176 microMxh) and day 12 (lactone: capsule = 22.1 microMxh, suspension = 6.1 microMxh; total: capsule = 1302 microMxh, suspension = 309 microMxh). The upper limit of the area under the curve of DRF-1042 (lactone and total) was higher under fed conditions (lactone = 15.9 microMxh, total = 605 microMxh) relative to fasted conditions (lactone = 8.53 microMxh, total = 393 microMxh) on day 1. One patient experienced stable disease. The toxicity and pharmacokinetics of the capsule correlated well with the suspension. The recommended phase II dose is 81 mg/m(2).

Safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally active novel camptothecin analog, DRF-1042, in refractory cancer patients in a phase I dose escalation study.

The objective of this study was to characterize the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and antitumor effects of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given for 5 consecutive days for 2 weeks, repeated every 3 weeks at 1.5 to 270 mg/m(2). Adverse events were monitored following NCI-CTC. Pharmacokinetics of lactone and total forms were determined using validated high-performance liquid chromatography (HPLC) and noncompartmental methods. Efficacy was evaluated applying World Health Organization (WHO) criteria. The 1st course was used to determine DLT and MTD. Twenty-five patients received 73 courses of therapy. Myelosuppression and diarrhea were DLTs. MTD was 120 mg/m(2)/day. AUC increased approximately linearly with dose. The t(1/2) for lactone and total forms was 9.9 and 29 hours, respectively. AUCs correlated significantly with nadir leucopenia and grade 4 diarrhea. Two complete responses (CRs) and 2 partial responses (PRs) were observed. In addition, 4 stable diseases were observed. The recommended phase II dose is 80 mg/m(2)/day.

Isolated central nervous system blast crisis in chronic myeloid leukemia.

Chronic myeloid leukemia is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome, t(9:22). Extramedullary blast crisis is a rare event. Imatinib mesylate has become the treatment of choice, especially for patients for whom allogenic stem cell transplantation is not an option. Imatinib produces complete cytogenetic responses in excess of 80%. However, the penetration of the drug and its metabolites into the CNS (Central Nervous System) is poor. Hence for patients who are on prolonged imatinib therapy and continue to have complete cytogenetic responses, the central nervous system may become a sanctuary site. We report a patient who had a complete hematologic and cytogenetic response and presented with headache and vomiting. The MRI showed meningeal enhancement and the CSF (Cerebro Spinal Fluid) examination was positive for blasts. He was started on cranial radiotherapy and triple intrathecal chemotherapy. He showed good symptomatic improvement and cleared the blasts in the CSF. At the end of radiation, he was in complete hematological remission but had 50% marrow metaphases positive for Philadelphia chromosome. As he did not have a matched sibling donor, the dose of imatinib was increased to 600 mg daily. He continues to be in complete hematologic remission at the time of this report.

Cytogenetic profile of chronic myeloid leukemias.

Chronic Myeloid leukemia is a clonal disease of multipotent haematopoietic cells associated with specific cytogenetic changes involving a translocation t(9;22) (q34:q11), more commonly known as Philadelphia Chromosome (Ph1). A total of 525 patients with CML (480 adults and 45 children) diagnosed at the Nizam's Institute of Medical Sciences, Hyderabad, formed the subjects of this study. Hematological investigations were carried out using standard methods. Unstimulated peripheral blood samples and/or bone marrow aspirates were used for cytogenetic analysis. Hematological evaluation at presentation showed that 435 were in chronic phase, 36 in accelerated phase and 54 in blast crisis. Chromosomal analysis revealed that 86.3% were Ph1 positive and 13.7% Ph1 negative. Additional chromosome changes observed during blast crisis included an extra Ph1 chromosome, Trisomy 8 and Trisomy 19. The results were correlated with survival pattern and prognosis of patients following certain treatment protocols.