Phase II trial of weekly docetaxel in second-line therapy for nonsmall cell lung carcinoma.

BACKGROUND: The authors conducted a Phase II study to evaluate the activity and toxicity of weekly docetaxel in second-line therapy for nonsmall cell lung carcinoma (NSCLC). METHODS: Patients with documented recurrent or refractory NSCLC, previously treated with no more than one chemotherapy regimen, were eligible if they had a performance status (PS) of 0-2, measurable or evaluable disease, and adequate organ function. Patients were treated with docetaxel 36 mg/m(2)/week for 6 consecutive weeks, administered intravenously with dexamethasone premedication. Cycles were repeated every 8 weeks. RESULTS: Thirty-one patients were enrolled. One patient was ineligible because of uncontrolled brain metastases. Hematologic toxicity was minimal. Nonhematologic toxicities were modest except for diarrhea and cumulative fatigue. There were no treatment-related deaths. The overall response rate was 10% (95% confidence interval [CI], 1.6-29%). The median survival time (MST) was 8.0 months. and the 1-year survival rate was 31% (95% CI, 17- 58%). Patients with PS 0-1 had a MST of 11.9 months with 1-year survival of 42%. CONCLUSIONS: Weekly docetaxel is very well tolerated as second-line therapy for NSCLC. The activity of this regimen appears to be comparable to the standard 3-week schedule. This regimen offers new opportunities for combination regimens, both as first- and second-line therapy for NSCLC.

Stage II and III-A non-small cell cancer of the lung: results of surgical resection at Fairfax Hospital.

Carcinoma of the lung is the single leading cause of death in patients with cancer and is responsible for over a quarter of all such deaths. Encouraging survival rates have been demonstrated following surgical resection of local (Stage I) disease. This paper details the results achieved with surgical resection of 100 patients with more advanced local--regional non-small cell carcinoma of the lung (Stages II and III-A). Operative (30-day) mortalities were 2.4% for Stage II patients and 8.5% for Stage III-A patients. Respective, 5-year Kaplan-Meier survival estimates were 41% (+/- 10%) and 36% (+/- 7%) and included all deaths, cancer-related as well as unrelated. When patients were stratified by stage, neither gender, age, cell type, tumor size, nor extent of resection proved statistically significant relative to long-term survival. However, Stage III-A patients, classified T-3 with contiguous tumor involvement of mediastinum, suffered a higher operative mortality and a significantly lower probability of long-term survival (p = 0.04). Finally, the results and appropriateness of prospective, clinical trials utilizing adjuvant therapies in Stage II and III-A patients and neo-adjuvant therapies in Stage III-A patients are discussed.

Resection for esophageal carcinoma at a Virginia hospital 1981-1989.

Between January 1, 1981 and December 31, 1989, 222 patients with carcinoma of the esophagus were seen at Fairfax Hospital. Fifty-eight (26.1%) underwent esophagogastrectomy. Operative (30-day) mortality was 8.6%. Follow-up was 98.3% complete. Of hospital survivors, 38 (76%) were resected for potential cure versus 12 (24%) for palliation. Consistent with the experience of others, a minority of patients (26%) presented with early (Stage I & II) disease; forty patients (69%) were noted to be Stage III or IV at time of resection and three patients (5%) were stage indeterminant. The five year Kaplan-Meier product limit survival estimate for Stage II patients was 52%, versus 22% for stage III, and 0% for Stage IV.

Stage I non-small cell cancer of the lung results of surgical resection at Fairfax Hospital.

Between January 1, 1981 and December 31, 1989, 2003 patients were evaluated at Fairfax Hospital with a diagnosis of carcinoma of the lung. Of these, 214 with Stage I non-small cell carcinoma underwent surgical resection. Operative (30-day) mortality was 1.4%. Overall 5-year survival was 59%, inclusive of all deaths, cancer-related as well as unrelated. Noting stage was constant, when patients were analyzed by gender, age, cell type, tumor status and extent of resection, only age proved statistically significant relative to long-term survival. However, even patients 70 and older averaged a nearly 50% 5-year survival. Moreover, if deaths are related to cancer only, 5-year survival rates should be significantly increased over the rates when quoted to all causes of death.

Inferior rectus recession for vertical tropia after cataract surgery.

Four patients with de novo onset of persistent vertical tropia ranging from 4 to 11 prism diopters (PD) after cataract surgery underwent inferior rectus recession. Deviations were stable and fuseable with prism preoperatively for 4 to 6 months. Three patients regained single binocular vision in all fields of gaze. Macular change developed in one eye of a diabetic patient, precluding adequate postoperative assessment. Mechanical and sensory factors, detailed assessment of pertinent preoperative findings, and intraoperative management are discussed. Previous literature is reviewed.

Dynamic and nonspecific dispersal of human T-cell leukemia/lymphoma virus type-I integration in cultured lymphoma cells.

The progression of HTLV-I proviral integration over a 3-year period of in vitro culture was examined in two human lymphoma lines, Hut 102 and MJ. Using specific HTLV-I molecular clones and a Southern analysis at different cell passages, Hut 102 increased from 2 to 19 integrated proviral integrations while MJ increased to at least 25 different integrations by passage 43. During the progress of increased superinfection and novel integration in vitro some of the previous proviral integrations were lost from the cultures. The 19 integrations of late passage Hut 102 cells were shown to be dispersed to 19 different human chromosomes by analysis of 34 distinct rodent X Hut 102 somatic cell hybrids which segregated human chromosomes (and included proviral integrations) in different combinations. The two primary integrations in Hut 102 were located on human chromosomes 4 and 20, respectively. A similar pattern of nonspecific integration was observed in somatic cell hybrid analysis of the 25 proviral integrations of MJ. The dynamic infection-reintegration process in vitro revealed in these studies may confuse experimental verification of potential cis acting functions of HTLV-I in the as yet poorly understood mechanism of neoplastic transformation.

Transactivation induced by human T-lymphotropic virus type III (HTLV III) maps to a viral sequence encoding 58 amino acids and lacks tissue specificity.

The acquired immune deficiency syndrome (AIDS) retrovirus, HTLV-III/LAV, encodes a transacting factor which directly or indirectly stimulates the expression of genes linked to its LTR. To further dissect this phenomenon, we have cotransfected a biologically active molecular clone of HTLV-III and a recombinant plasmid containing an indicator gene, the bacterial gene for chloramphenicol acetyltransferase (CAT), under the control of the HTLV-III LTR. Amplified CAT activity was detected in both lymphoid cells and fibroblasts from a number of species in the presence of the proviral DNA. Deletion experiments confirm the previous assignment of the gene required for transactivation to a region immediately 5' to the envelope gene, and further narrow down the critical functional domain to a coding sequence of 58 codons.

Gene for T-cell growth factor: location on human chromosome 4q and feline chromosome B1.

T-cell growth factor (TCGF) or interleukin-2 (IL-2), an immunoregulatory lymphokine, is produced by lectin- or antigen-activated mature T lymphocytes and in a constitutive manner by certain T-cell lymphoma cell lines. By means of a molecular clone of human TCGF and DNA extracted from a panel of somatic cell hybrids (rodent cells X normal human lymphocytes), the TCGF structural gene was identified on human chromosome 4. In situ hybridization of the TCGF clone to human chromosomes resulted in significant labeling of the midportion of the long arm of chromosome 4, indicating that the TCGF gene was located at band q26-28. Genomic DNA from a panel of hybrids prepared with HUT-102 B2 cells was examined with the same molecular clone. In this clone of cells, which produces human T-cell leukemia virus, the TCGF gene was also located on chromosome 4 and was apparently not rearranged. The homologous TCGF locus in the domestic cat was assigned to chromosome B1 by using a somatic cell hybrid panel that segregates cat chromosomes. Linkage studies as well as high-resolution G-trypsin banding indicate that this feline chromosome is partially homologous to human chromosome 4.

The control of chemotherapy-induced emesis.

Nausea and vomiting are frequent and serious toxicities of cancer chemotherapy that have been largely ignored in the past. Recently there has been renewed interest in this significant problem, with important advances in understanding the physiology of vomiting and a burgeoning number of clinical trials that use newer classes of antiemetics. At present phenothiazines are the only class of antiemetics that have shown both efficacy and safety in large numbers of cancer patients, but they are inadequate against strongly emetic agents such as cisplatin. New agents and new approaches have shown promise but need additional testing before they can be recommended for routine use.