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At least 577 records · Page 32Linked to original sources
PubMed1986

Investigation of the additive potential of teniposide and vincristine in non-Hodgkin's lymphoma. Australian and New Zealand Lymphoma Group.

Two hundred forty-seven patients with non-Hodgkin's lymphoma were randomized to receive doxorubicin, cyclophosphamide, and prednisolone in combination with vincristine (ACVP) or teniposide (ACTP) or both vincristine and teniposide (ACTVP). ACVP produced 44% complete remissions (CRs) and 32% partial remissions (PRs), whereas ACTP produced 46% CRs and 33% PRs and ACTVP produced 47% CRs and 36% PRs. Survival and relapse-free survival were also comparable for the three arms. The majority (59%) of patients had diffuse large cell lymphoma. Within this group, CR was achieved in 52% and no significant difference was observed in the response rates, survival, or relapse-free survival for the three treatment arms. Toxic effects occurred with equivalent frequency in the three regimens, except for neurotoxicity and myelosuppression. Moderate to severe neurotoxicity occurred in 20% of ACTVP-treated patients and in 8% of ACVP-treated patients but was not seen in any of the ACTP-treated patients (P = 0.0004). Severe myelosuppression occurred in 27% of ACTVP-treated patients and in 22% of ACTP-treated patients but only in 8% of ACVP-treated patients (P = 0.02), indicating an increased risk of myelosuppression for the combinations including teniposide. These results confirm our previous findings that teniposide can replace vincristine in the treatment of non-Hodgkin's lymphoma, with freedom from neurotoxicity and comparable survival and response rates. However, the combined use of teniposide and vincristine in the schedule as described has not increased response rates or survival but has instead added to neurotoxicity.

Actuarial Analysis↗
PubMed1985

[Disorders of nocturnal sleep in Huntington chorea].

A polygraphic study of nocturnal sleep was conducted in 11 patients with Huntington's chorea. It was found that Stage I sleep and the phase of rapid sleep (PRS) were prolonged while delta-sleep was considerably shortened. This was accompanied by an increase in the latent periods of all stages of slow sleep and the shortening of the latent period of PRS. The patients displayed a tendency toward an increased number of sleep spindles and a considerable decrease in the delta-index. Patients with Huntington's chorea showed an increase in body movements during sleep. Dissociations were detected in polygraphic characteristics of individual phases of sleep. The reduction of delta-sleep is related to cerebral cortex atrophy while the increase in PRS is explained by neurotransmitter disturbances characteristic of this disease.

Adult↗
PubMed1986

Postnatal development of renin-angiotensin system in rats.

The changes occurring in several components of the rat renin-angiotensin system (RAS) were studied for the brief postnatal period, between the fourth and tenth week of life. The parameters were: plasma renin activity (PRA), plasma renin concentration (PRC), plasma renin substrate (PRS) and the plasma angiotensin II concentration (AII). A gradual decrease in PRA with age was noticed. Between the fourth and the eighth weeks of life, this was attributed to a corresponding decline in both PRC and PRS. However, between the eighth and tenth weeks, no changes in PRA could be detected, but PRC and PRS increased, perhaps as a consequence of the changes in renal function and the AII increase observed. In this second period, simultaneously with the RAS changes described, there was reduced sodium chloride excretion as the glomerular filtration rate (GFR) stabilized. The data presented suggest that this postnatal period is critical, in rats, for the maturation of the RAS component control mechanisms; they appear to be closely related to the development of the renal function.

Angiotensin II↗
PubMed1985

Covalent modification of phenylalanyl-tRNA synthetase with phenylalanine during the amino acid activation reaction catalyzed by the enzyme.

Yeast phenylalanyl-tRNA synthetase (PRS) is shown to undergo autoaminoacylation with phenylalanine under in vitro amino acid activation conditions. Phenylalanyl adenylate enzyme complex yields a covalent phenylalanyl isopeptide exclusively with the beta subunit of the alpha 2 beta 2 enzyme. Contrary to previously reported cases of autoaminoacylation of aspartyl-tRNA synthetase and tryptophanyl-tRNA synthetase, the autoaminoacylation of PRS occurs under a specific set of conditions and results in the identification of only one labeled tryptic peptide on two types of high pressure liquid chromatography columns. The ability of PRS to undergo this covalent modification directly correlates with its ability to catalyze the synthesis of diadenosine 5',5"'-P1,P4-tetraphosphate from enzyme-bound phenylalanyl adenylate. Both reactions require the presence of low levels of zinc or cadmium and are inhibited by tRNAPhe or by low levels of low molecular weight thiols. Since diadenosine 5',5"'-P1,P4-tetraphosphate synthesis is known to be catalyzed in vivo in response to oxidation stress, it is also likely that the autoaminoacylation of phenylalanyl-tRNA synthetase may occur in vivo under a similar set of conditions. These reactions are thus not simply the result of accumulation of phenylalanyl adenylate and probably reflect conformational changes in the protein which are brought about by its interaction with zinc or cadmium.

Amino Acyl-tRNA Synthetases↗
PubMedDate not supplied

Phase II trials with cis-dichlorodiammineplatinum(II) in the treatment of urothelial cancer.

Results of disease-oriented phase II trials with cis-dichlorodiammineplatinum(II) (cis-platinum) in 135 adequately treated patients with advanced urothelial tumors at Memorial Sloan-Kettering Cancer Center are presented. In four protocols which used cis-platinum alone or in combination with Adriamycin and/or cyclophosphamide in 95 patients with bladder cancer, no significant difference (46%--54%) in the number of partial remissions (PRs) in previously untreated patients was noted. The median duration of response in three of the four protocols was 5--7 months. A review of the literature indicates that cis-platinum used singly produced remissions in 45% of 67 patients (95% confidence limit, 12%--57%). In the treatment of superficial bladder tumors, intravesically administered cis-platinum induced few complete or sustained remissions. The difficulties in evaluating response with intravesical therapy are discussed. The importance of patient selection, particularly the need to include patients with objectively measurable disease parameters, in phase II trials is stressed. Differences in patient characteristics and response criteria will necessitate prospective randomized trials of cis-platinum alone versus cis-platinum combination regimens in the treatment of metastatic disease. cis-Platinum was inactive (12% PRs) in 25 patients with prostatic cancer who had objectively measurable parameters. It is of interest that PRs were obtained in three of six patients (50%) with penile cancer. A review of the literature and the data in the present series indicates that cis-platinum has no value in the treatment of metastatic hypernephroma.

Antineoplastic Agents↗
PubMedDate not supplied

Phase II evaluation of cis-dichlorodiammineplatinum(II) in advanced malignancies of the genitourinary and gynecologic organs: a Southwest Oncology Group Study.

One hundred and forty-seven fully and partially evaluable patients with advanced measurable malignancies of the genitourinary and gynecologic organs were given cis-dichlorodiammineplatinum(II) at a dose of 75 mg/m2 iv every 3 weeks. Thirty-six patients with testicular neoplasms were studied; five complete responses (13.9%) and seven partial responses (PR) (19.4%) were noted. Thirty-seven patients with ovarian adenocarcinoma were evaluated; five PRs (13.5%) were seen. One complete response (11.1%) and two PRs (22.2%) were obtained among nine patients with urinary bladder cancer. Four PRs (19.0%) were seen among a group of 21 patients with advanced prostate cancer. One PR (4.8%) was noted among 21 patients with renal cell cancer and no responses were seen in eight patients with cervical cancer. There was a highly statistically significant (P less than 0.001) survival advantage for the responding testicular tumor patients. Toxicity was similar to that previously reported, with gastrointestinal side effects and nephrotoxicity most commonly seen. Prospective and sequential analysis of renal function provided strong evidence for cumulative nephrotoxicity in these patients given bolus injections of cis-dichlorodiammineplatinum(II) without prehydration or treatment with fuosemide or mannitol.

Cisplatin↗
PubMed1982

[Propranolol effect on renin-angiotensin system kinetics during experimental hyperthyroidism (author's transl)].

The basal levels of angiotensin I (A. I), plasma renin activity (PRA), plasma renin substrate (PRS) and plasma renin concentration (PRC) were estimated in hyperthyroid rats before and after propranolol treatment. Serum levels of triiodothyronine (T3), thyroxine (T4), angiotensin I both basal and generated by incubation of plasma samples were measured by radioimmunoassay, while, PRC and PRS were evaluated by triiodothyronine or thyroxine treatment induced a decrease in PRS and an increase in PRC whereas triiodothyronine alone produced an increase in the basal levels of angiotensin I and PRA. The propranolol in euthyroid animals not only decreased the basal levels of angiotensin I and PRA, but also prevented the PRC increase in hyperthyroid rats, while restoring at the same time the basal levels of angiotensin I and PRA.

Angiotensin I↗
PubMed1981

[Experimental study on ego functions of the blind: plastics Rorschach techniques (1) (author's transl)].

UNLABELLED: Plastics Rorschach stimuli (PRS) were produced through the same randamization procedure as the Rorschach figures. Ego functions of the blind may be studied by the use of PRS to which even the complete blind can respond. METHOD: Subjects of normal visual acuity are 39 (22 males) and blind subjects 24 (20 males). Results : Differences between the eye mask condition and visual condition and between the group of normal visual acuity and the group of the blind were studied. These two results were compared with each other. Conculsions: PRS is one of the useful means to study the blind's ego functions as well as the roles of dermal sensation and visual perception in ego functions in general.

Adolescent↗
PubMed1995

Autoantibodies in Parry-Romberg syndrome: a serologic study of 14 patients.

OBJECTIVE: To determine autoantibody profiles of patients with Parry-Romberg syndrome (PRS). METHODS: Antinuclear antibodies (ANA) in 14 patients with PRS were studied by indirect immunofluorescence (IIF), immunodiffusion and immunoblotting. Antinative DNA antibodies and rheumatoid factor (RF) were also analyzed. RESULTS: ANA were positive in 8 patients (57%). The patterns of staining included nucleolar, nuclear speckled and homogeneous. Anticentromere antibodies were observed in 2 and antihistone antibodies in 3 sera. Rheumatoid factor was found in 5 (36%) sera. Antinative DNA or antibodies that precipitated rabbit thymus extract were not found in any patients. CONCLUSION: The serologic abnormalities observed in this study suggests that autoimmunity could play a pathogenic role in PRS.

Adolescent↗
PubMed1994

A novel 39-kDa phosphoribosylpyrophosphate synthetase-associated protein of rat liver. Cloning, high sequence similarity to the catalytic subunits, and a negative regulatory role.

The rat liver phosphoribosylpyrophosphate (PRPP) synthetase exists as complex aggregates composed of the 34-kDa catalytic subunits (PRS I and II) and other 39- and 41-kDa proteins (Kita, K., Otsuki, T., Ishizuka, T., and Tatibana, M. (1989) J. Biochem. (Tokyo) 105, 736-741), which are termed here PRPP synthetase-associated proteins (PAPs). We have cloned the cDNA for the major one of 39 kDa (PAP39) from a rat liver cDNA library. Nucleotide sequencing showed that the clone encoded 356 amino acids containing sequences of all five peptides derived from PAP39. Surprisingly, the deduced amino acid sequence is markedly similar to those of the 34-kDa catalytic subunits. Excluding two regions (about 45 residues in total), PAP39 has a 48% identity with PRS I. Northern analysis detected a major 1.9-kilobase transcript in all 16 rat tissues examined, and the relative amounts of PAP39 mRNA to PRS I mRNA varied with tissues. Covalent cross-linking experiments gave definitive evidence for molecular interaction of PAP39 with the catalytic subunits. Immunoprecipitation experiments revealed that all the catalytic subunits existed as complexes containing PAP39. When PAPs were eliminated from the rat liver enzyme complex by gel filtration in the presence of 1 m MgCl2, a lyotrope, or by mild tryptic treatment, the enzyme activity of the remaining catalytic subunits increased. Based on these results, we propose that PAP39, the major component of PAPs, plays a negative regulatory role in PRPP synthesis and hence is an important factor controlling nucleotide syntheses in general.

Amino Acid Sequence↗
PubMed1994

Kinetic and modeling studies of subsites S4-S3' of Moloney murine leukemia virus protease.

The substrate specificity of the Moloney murine leukemia virus protease (Mo-MuLV PR) was analyzed by using the oligopeptide substrate Val-Ser-Gln-Asn-Tyr decreases Pro-Ile-Val-Gln-NH2 and a series of analogs containing single amino acid substitutions in the P4-P3' positions. Mo-MuLV PR appears to act similarly to the human immunodeficiency virus (HIV) PRs, except for peptides having substitutions at P4 and P2 positions. Mo-MuLV PR shows a strong preference for the analogs having hydrophobic residues, such as Val or Ile at P4, and Ile and Leu at P2, in contrast to HIV-1 and HIV-2 PRs, which prefer smaller or more polar residues at both positions. We built a molecular model of Mo-MuLV PR on the basis of the crystal structure of the related HIV PR. Although the overall structure of Mo-MuLV PR is predicted to be close to that of HIV-1 PR, almost all of the residues forming the subsites are different. The increased hydrophobicity due to the Pro12 insertion and the presence of more aromatic residues in the S4 subsite of Mo-MuLV PR compared to HIV-1 and HIV-2 PRs can be correlated with the observed differences using P4-substituted analogs of VSQNYPIVQ. The preference of Mo-MuLV PR for larger hydrophobic residues at the P2 position can be correlated with the larger size of its S2 subsite, due in part to the presence of Val39, Ala57, and His84 in Mo-MuLV PR, instead of Ile32, Ile50, and Met76, respectively, as occurs in HIV-2 PR.

Amino Acid Sequence↗
PubMed1998

Pathologic rupture of the spleen as the initial manifestation of acute lymphoblastic leukemia: an additional case.

Pathological rupture of the spleen (PRS) is a rare, but well known complication of some hematological malignancies. In a recent review of the literature, Giagounidis et al. Identified 136 cases of pathologic rupture of the spleen since 1861. This number gives an idea of how seldom it occurs. In this review, 34% of the cases had occurred in acute leukemias, and 13% in acute lymphoblastic leukemias. In most cases, PRS occurs on the course of the disease. PRS as initial manifestation of ALL is a very rare feature: only six cases have been reported in the literature. Before now, in our hospital, we had only seen one case of a patient suffering from chronic myelomonocytic leukemia who presented splenic rupture as the initial manifestation of this disease. We now describe the seventh case, to our knowledge, of acute lymphoblastic leukemia presenting as pathologic splenic rupture.

Humans↗
PubMed1998

Induction of progestin receptors by estradiol in the forebrain of estrogen receptor-alpha gene-disrupted mice.

Mice, rats, and humans have two types of estrogen receptors, estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). Estrogen receptor-alpha gene-disrupted (ERalpha-disrupted) mice bear two nonfunctional copies of the ERalpha gene. This mutation blocks the synthesis of full-length ERalpha, renders the animals infertile, and inhibits the induction of female sexual behaviors by estradiol and progesterone. It is likely that many of the processes contributing to the regulation of sexual receptivity by estradiol and progesterone are compromised in ERalpha-disrupted mice. However, given the importance of progesterone in the regulation of sexual receptivity and given the importance of progestin receptors (PRs) in mediating the responses of females to progesterone, we investigated the effects of ERalpha disruption on the induction of PRs by estradiol in the forebrain. We hypothesized that estradiol would induce PRs in wild-type mice but not in ERalpha-disrupted mice. Ovariectomized wild-type and ERalpha-disrupted mice were implanted with either estradiol-filled capsules or empty capsules for 5 d, after which their brains were processed for the immunocytochemical detection of PR. Estradiol increased the number of PR-immunoreactive cells in both wild-type and ERalpha-disrupted mice. The residual responsiveness of ERalpha-disrupted mice to estradiol could be accounted for by an ERbeta-dependent mechanism or another as yet unidentified estrogen receptor; however, because ERalpha-immunoreactivity and PCR product representing the 3' end of ERalpha mRNA were found in at least one PR-containing region of the ERalpha-disrupted mice, an ERalpha splice variant may also mediate the induction of PR-immunoreactivity in ERalpha-disrupted mice.

Animals↗
PubMed1999

Phase II trial of chemotherapy with 5-fluorouracil, bleomycin, epirubicin, and cisplatin for patients with locally advanced, metastatic, or recurrent undifferentiated carcinoma of the nasopharyngeal type.

BACKGROUND: The aim of this study was to evaluate the toxicity and efficacy of the combination of 5-fluorouracil, bleomycin, epirubicin, and cisplatin (FBEC) in the treatment of patients with undifferentiated carcinoma of nasopharyngeal type (UCNT). The study included patients with metastatic or recurrent disease (Group A) and previously untreated patients with locally advanced nonmetastatic disease (T >/= 3 or any T, N >/= 2, M0, according to 1987 criteria of the International Union Against Cancer and the American Joint Committee on Cancer (Group B). METHODS: From January 1992 to November 1996, 49 patients with histologically proven UCNT were treated with intravenous (i.v.) 5-fluorouracil (700 mg/m(2)/day by continuous infusion for 4 days), epirubicin (70 mg/m(2) i.v. on Day 1), Bleomycin (10 mg i.v. bolus on Day 1 followed by 12 mg/m(2)/day by continuous infusion for 4 days), and cisplatin (100 mg/m(2) on Day 5); this regimen was repeated every 21 days. Six cycles were given to Group A (26 patients), with bleomycin omitted during the last 3 cycles. In Group B (23 patients), only 3 cycles were given, followed by conventional radiotherapy (70 gray for 7 weeks). RESULTS: Of the 26 patients entered in Group A, 23 were evaluable for response. Nine complete responses (CRs) and 9 partial responses (PRs) were assessed, for a 78% objective response rate (ORR) (95% CI: 56-92). Three patients are alive with no evidence of disease after 43, 61, and 73 months, respectively. These patients achieved a CR with chemotherapy followed by consolidating radiotherapy to their target lesions. In Group B, the ORR was 91.5%, with 5 CRs (22%) and 16 PRs (69.5%) assessed in the 23 patients. Three months after the end of radiotherapy, the ORR was 87% (20 patients). After a median follow-up of 51 months (range, 24-67 months), 15 patients (65%) are alive without evidence of disease. Forty percent of cycles (51% in Group A, 25% in Group B) resulted in Grade 4 neutropenia, with fever and/or sepsis in 9.5%. Mucositis was seen in 42% of pretreated patients. There were 3 treatment-related deaths (2 from complications of infection and 1 bleomycin fibrosis at a total dose of 160 mg/m(2)), all of them in Group A. CONCLUSIONS: The FBEC regimen has good activity, with durable responses in patients with locally advanced, metastatic, or recurrent UCNT. This regimen is safe for patients with locally advanced disease, but close follow-up and supportive measures are needed when it is used to treat those with metastatic or recurrent disease.

Adolescent↗
PubMed1986

The activity of a single-agent 5-fluorouracil infusion in advanced and recurrent head and neck cancer.

Although chemotherapy regimens using cisplatin (CDDP) and 5-fluorouracil (5-FU) infusion have shown significant activity in advanced and recurrent head and neck cancer, their use requires normal renal function. The use of 5-FU infusion alone has not been evaluated in these tumors. Retrospective analysis revealed 11 patients who received 5-FU infusion alone because of poor renal function: 7 patients with recurrent disease who were previously treated with surgery and/or radiation therapy and 4 patients who received 5-FU as preoperative induction therapy for advanced disease were treated. The infusion dose consisted of 1000 mg/M2/24 hours for 96 hours for patients with previous radiation and 120-hour infusions for patients without previous radiation. The courses were repeated at 3-week intervals. Eight of 11 (72%) demonstrated a response (1 complete response [CR] and 7 partial responses [PRs]. Responses occurred in 4 of 4 (all PRs) patients with previously untreated epidermoid cancer, 1 patient with recurrent adenocystic cancer, and 3 of 6 patients with recurrent epidermoid cancer not previously treated with chemotherapy. Three patients, with no prior systemic or local therapy, who were clinical partial responders to 5-FU infusion went on to surgery and radiotherapy. Their responses were maintained for 18, 14, and 46+ months, respectively. The predominant toxicities were stomatitis (6/11, 55%) and leukopenia (2/11 patients). In this retrospective analysis, 5-FU infusion alone demonstrated good activity in head and neck cancer with tolerable toxicity. Since the number of patients is small and were selected on the basis of renal function, prospective evaluation is essential.

Aged↗
PubMed1994

Evaluation of low dose continuous infusion 5-fluorouracil in patients with advanced and recurrent renal cell carcinoma. A Southwest Oncology Group Study.

BACKGROUND: The response rate of metastatic renal cell cancer to cytotoxic therapy over the last 10 years has been 5.6%. Low dose continuous 5-fluorouracil (5-FU) has demonstrated efficacy in other cytotoxic refractory tumors, such as pancreas, colorectal, and recurrent breast. The Southwest Oncology Group undertook a Phase II trial of low dose, continuous 5-FU in metastatic renal cell cancer. METHODS: Sixty-one patients were entered in the study to receive 300 mg 5-FU/m2/day for 7 days via a central venous catheter and external programmable pump. The pump was refilled every 7 days. Pyridoxine (50 mg, orally) was administered prophylactically three times a day. RESULTS: A response of 5.2% (one complete response [CR] and two partial responses [PRs]) was achieved. The overall survival was 12 months. The duration of the CR is more than 30 months. Both PRs lasted 6 months. No survival advantage was noted with either prior nephrectomy or biologic therapy. The majority of toxicities were Grade 2: anemia, anorexia, diarrhea, nausea/vomiting, and stomatitis. No toxic deaths occurred. CONCLUSION: Low dose, continuous 5-FU demonstrated minimal activity in metastatic renal cancer.

Carcinoma, Renal Cell↗
PubMed1994

Total body irradiation and prednimustine in chronic lymphocytic leukemia and low grade non-Hodgkin's lymphomas. A 9-year experience at a single institution.

BACKGROUND: The efficacy and toxicity of total body irradiation (TBI) in patients with chronic lymphocytic leukemia (CLL) and low grade non-Hodgkin's lymphomas (NHL) were evaluated. METHODS: Between January 1984 and September 1992, 81 consecutive patients, 40 affected with CLL and 41 with low grade NHL, with symptomatic Stage III and IV disease, were treated with TBI followed by prednimustine. TBI was given with a 6 MV linear accelerator, applying two opposite alternating fields, including total body, with two fractions of 15 cGy given per week (3-day interval). A total dose of 150 cGy was given over 5 weeks. Six to nine courses of prednimustine (100 mg/m2 orally for 5 consecutive days every 4 weeks) was administered 2 months after TBI treatment as consolidation therapy. RESULTS: Of 40 patients with CLL, 18 (Group I; median age 58.5 years) were younger than 65 years and 22 (Group II; median age 73 years) were older. The overall response rates were 78% in Group I and 91% in Group II, with a median response time of 16.5 and 16 months, respectively. Hematologic toxicity was 72% in Group I and 73% in Group II. It was reversible in all but one heavily pretreated patient who died of progressive anemia and thrombocytopenia after TBI alone. In the 40 patients with CLL, the response rate was 85%; there were 5 complete responses (CRs) (12.5%) and 29 partial responses (PRs) (72.5%). Of the 41 patients with NHL, 29 (Group I; median age 55 years) were younger than 65 years and 12 (Group II; median age 71.5) were older. The overall response rate in both groups was 83%, with median response times of 18.5+ and 14.5+ months for Groups I and II, respectively. Hematologic toxicity was 59% in Group I, whereas it was 50% in Group II. It was reversible in all patients. Overall, in the 41 patients with symptomatic Stage III and IV low grade NHL, the response rate was 82.8%; there were 10 CRs (24.3%) and 24 PRs (58.5%). The prednimustine regimen was generally well tolerated. CONCLUSIONS: In our experience, TBI given in a dose of 150 cGy in 10 fractions twice a week, followed by prednimustine, is an effective treatment for patients with CLL and patients with low grade NHL. This treatment also is effective in patients older than 65 years. The toxicity is acceptable, particularly when TBI and prednimustine are given as initial treatment. Pretreated patients should be monitored strictly.

Age Factors↗
PubMed2001

Sequential combination chemotherapy in patients with advanced nonsmall cell lung carcinoma: carboplatin and gemcitabine followed by paclitaxel.

BACKGROUND: The objective of this Phase II study was to evaluate the concept of sequential chemotherapy in the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC) by the administration of carboplatin plus gemcitabine followed by of paclitaxel. METHODS: Patients with Stage IIIB (pleural effusion) or Stage IV NSCLC and a Southwest Oncology Group (SWOG) performance status (PS) of 0--2 were eligible. Therapy consisted of three cycles of carboplatin (area under the concentration-time curve = 5.5 mg/mL per minute) on Day 1 and gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days followed by three cycles of paclitaxel 225 mg/m(2) every 21 days. RESULTS: Of the 37 eligible patients, 81% had Stage IV disease, and 27% had a PS of 2; all were assessable for survival and toxicity; 32 patients were assessable for response. After treatment with carboplatin plus gemcitabine, there were no complete responses (CRs) and eight partial responses (PRs) (response rate [RR], 25%; 95% confidence interval [95% CI], 11--43%). The best overall response was two CRs and eight PRs (RR, 31%; 95% CI, 16--50%). The median survival time was 9.5 months, the 1-year survival rate was 36% (95% CI, 26--44%), the 2-year survival rate was 11% (95% CI, 3--25%), and the median time to disease progression was 4.9 months. The median survivals were 11.2 months for patients with a PS of 0--1 and 6.4 months for patients with a PS of 2. Noncumulative, reversible thrombocytopenia was the principal toxicity with carboplatin/gemcitabine therapy. Paclitaxel therapy was well tolerated, and moderate (Grade 3) neutropenia was the primary toxic effect. One cardiac death occurred, possibly related to paclitaxel. CONCLUSIONS: This study is the first to evaluate planned sequential chemotherapy in patients with NSCLC. Carboplatin plus gemcitabine followed by paclitaxel was well tolerated and resulted in promising survival in this patient population. This pilot experience forms the basis for an ongoing SWOG trial. Cancer 2001;92:146-52. Published 2001 American Cancer Society.

Aged↗