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Biomedical subjects

S Sambandam

Publications and source records attributed to S Sambandam.

8 recordsLinked to original sources

Phase I trial of weekly paclitaxel in advanced lung cancer.

PURPOSE: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose (MTD) of paclitaxel using an extended weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/microL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. RESULTS: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle 1. Neutropenia was dose-limiting. Fourteen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% +/- 10%) patients demonstrated an objective response. CONCLUSION: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

Adult↗

A patient with myelodysplastic syndrome studied by GTG-banding and fluorescent in situ hybridization (FISH).

Molecular cytogenetics using fluorescent in situ hybridization (FISH) is an extremely useful adjunct technique to conventional cytogenetics via GTG-banding. The present paper illustrates the utility of FISH by describing a patient with myelodysplastic syndrome (MDS) who was initially studied using GTG-banding and whose bone marrow was found to be populated with hyperdiploid cells. FISH was used to delineate the numerical and structural chromosomal abnormalities. It revealed the presence of trisomy 8 and determined that the previously unidentifiable marker chromosome was of chromosome 10 origin. Although trisomy 8 is a frequent finding in MDS, the structural chromosomal abnormality of chromosome 10 as reported here is not a common finding.

Aged↗

Weekly paclitaxel in patients with advanced lung cancer: preliminary data from a phase II trial.

We conducted a phase II trial in chemotherapy-naive patients with advanced non-small cell lung cancer to determine the efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) delivered at a maximum tolerated dose of 175 mg/m2 on an extended weekly schedule. Patients with stage IIIB/IV non-small cell lung cancer were eligible if they had an Eastern Cooperative Oncology Group performance status of 0 to 2, had received no previous chemotherapy, demonstrated normal hematologic and hepatic function, and could provide informed consent. Paclitaxel 175 mg/m2 was administered as an intravenous infusion weekly over 3 hours with standard premedication, for 6 weeks of an 8-week cycle. Doses were modified for absolute neutrophil count less than 1.5 x 10(9)/L or neuropathy greater than grade I on the day of therapy. Patients without progressive disease received subsequent cycles at the same dose. To date, 30 patients have been enrolled; data are available for 25. The median age was 65 years (range, 38 to 78 years), 23 patients were performance status 0 or 1, and 14 had received prior radiation. Sites of disease included the lung (23 patients), central nervous system (11), bone (seven), liver (one), kidney (one), and soft tissue (eight). Eighty-three percent, 75%, 58%, and 50% of intended doses were delivered during cycles 1 though 4, respectively. Grade 2/3 neuropathy occurred in nine patients, but improved in all nine following dose reduction. Grade 3/4 neutropenia occurred in 10 patients. Partial responses occurred in 14 of 25 patients (56%; 95% confidence interval, 46% to 66%). Median duration of response was 6.5 months, and the 1-year survival rate was 53%. The extended weekly paclitaxel schedule results in enhanced dose intensity, marked activity, and acceptable toxicity. Paclitaxel given weekly at maximum dose intensity may be more effective than conventional paclitaxel administration schedules.

Adult↗

Systemic mast cell disease presenting with peripheral blood eosinophilia.

Patients with mast cell disease most frequently present with skin lesions (urticaria pigmentosa), with systemic involvement in many cases. However, a small subset of patients with systemic mast cell disease lacks skin lesions and, in these patients the correct diagnosis may be difficult to establish. Patients with systemic mast cell disease commonly have hematologic abnormalities, including eosinophilia in up to 20% of cases, but isolated eosinophilia has been reported rarely. We describe an 82-year-old woman who was admitted to Rhode Island Hospital for coronary artery disease and unstable angina. Incidentally, an absolute eosinophil count of 7.84 x 10(9)/L (normal, < 0.45 x 10(9)/L) was detected with moderate thrombocytopenia and mild anemia. Review of earlier records revealed that absolute eosinophilia had been present for approximately 4 months, initially without other hematologic abnormalities. Clinical work-up showed left upper quadrant tenderness. No skin lesions were identified. Bone marrow core biopsy revealed paratrabecular, perivascular, and medullary mast cell aggregates with eosinophils, suggestive of mast cell disease. At autopsy the diagnosis was confirmed. Mast cell aggregates were found in the liver, spleen, lymph nodes, and bone marrow, and chloroacetate esterase stain highlighted mast cell granules. The bone marrow was also hypercellular with granulocytic and eosinophilic hyperplasia, suggestive of a poorly defined myeloproliferative disorder. Patients with systemic mast cell disease initially may present with peripheral eosinophilia. Clinical suspicion of the diagnosis facilitates proper handling of the bone marrow core biopsy specimen to allow the demonstration of mast cell granules.

Aged↗

A clinical study of adult leukaemias.

The incidence of adult leukaemias, their response to therapy and the complications of therapy were studied in 121 cases over seven years (1981-1987). All cases were followed up till recovery or death for periods ranging from seven days to seven years. Adult leukaemias accounted for 2.56% of all admissions due to malignancies. There were 21 cases of acute lymphoblastic leukaemia, 61 of acute myelogenous leukaemia, 36 of chronic myelocytic leukaemia and 3 chronic lymphocytic leukaemia. All received aggressive combination chemotherapy. Remission could be achieved in 57% to 60% of cases. Infection (34%), bleeding (34%), and central nervous system involvement (25%) were the complications during therapy. The cause of death was ascertained in 87 of 90 deaths by a detailed postmortem. Haemorrhage (34.5%), infection (31%) and uncontrolled leukaemia (22%) were the leading causes, either singly or in combination. Some of the uncommon causes of death were fulminant hepatic failure, coronary artery disease, gangrene of the colon and disseminated tuberculosis.

Adolescent↗