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1.
Breast Cancer Res Treat ; 164(2): 461-466, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28451965

ABSTRACT

PURPOSE: Early-stage hormone-receptor positive breast cancer is treated with endocrine therapy and the recommended duration of these treatments has increased over time. While endocrine therapy is considered less of a burden to patients compared to chemotherapy, long-term adherence may be low due to potential adverse side effects as well as compliance fatigue. It is of high clinical utility to identify subgroups of breast cancer patients who may have excellent long-term survival without or with limited duration of endocrine therapy to aid in personalizing endocrine treatment. METHODS: We describe a new ultralow risk threshold for the 70-gene signature (MammaPrint) that identifies a group of breast cancer patients with excellent 20 year, long-term survival prognosis. Tumors of these patients are referred to as "indolent breast cancer." We used patient series on which we previously established and assessed the 70-gene signature high-low risk threshold. RESULTS: In an independent validation cohort, we show that patients with indolent breast cancer had 100% breast cancer-specific survival at 15 years of follow-up. CONCLUSIONS: Our data indicate that patients with indolent disease may be candidates for limited treatment with adjuvant endocrine therapy based on their very low risk of distant recurrences or death of breast cancer.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/mortality , Gene Regulatory Networks , Cohort Studies , Female , Genetic Predisposition to Disease , Humans , Kaplan-Meier Estimate , Precision Medicine , Prognosis , Risk Assessment , Survival Rate
2.
Ann Oncol ; 27(6): 1013-1019, 2016 06.
Article in English | MEDLINE | ID: mdl-26961146

ABSTRACT

BACKGROUND: The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy. PATIENTS AND METHODS: This analysis evaluated pooled data from two phase I trials [NCT00516373 (study 2); NCT00777582 (study 24)] and four phase II trials [NCT00494442 (study 9); NCT00628251 (study 12); NCT00679783 (study 20); NCT01078662 (study 42)] that recruited women with relapsed ovarian, fallopian tube or peritoneal cancer. All patients had a documented gBRCAm and were receiving olaparib 400 mg monotherapy twice daily (capsule formulation) at the time of relapse. Objective response rate (ORR) and duration of response (DoR) were evaluated using original patient outcomes data for patients with measurable disease at baseline. RESULTS: Of the 300 patients in the pooled population, 273 had measurable disease at baseline, of whom 205 (75%) had received ≥3 lines of prior chemotherapy. In the pooled population, the ORR was 36% [95% confidence interval (CI) 30-42] and the median DoR was 7.4 months (95% CI 5.7-9.1). The ORR among patients who had received ≥3 lines of prior chemotherapy was 31% (95% CI 25-38), with a DoR of 7.8 months (95% CI 5.6-9.5). The safety profile of olaparib was similar in patients who had received ≥3 lines of prior chemotherapy compared with the pooled population; grade ≥3 adverse events were reported in 54% and 50% of patients, respectively. CONCLUSION: Durable responses to olaparib were observed in patients with relapsed gBRCAm ovarian cancer who had received ≥3 lines of prior chemotherapy. CLINICALTRIALSGOV: NCT00516373; NCT00494442; NCT00628251; NCT00679783; NCT00777582; NCT01078662.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Ovarian Neoplasms/drug therapy , Phthalazines/administration & dosage , Piperazines/administration & dosage , Adult , Aged , Clinical Trials as Topic , Disease-Free Survival , Female , Germ-Line Mutation , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Phthalazines/adverse effects , Piperazines/adverse effects , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects
3.
Gynecol Oncol ; 140(2): 199-203, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26723501

ABSTRACT

OBJECTIVE: The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.govNCT01078662) have been reported previously. METHODS: Eligible patients were treated with oral olaparib 400mg bid capsule monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for patients with measurable disease at baseline. Safety and tolerability were assessed for all patients by adverse event (AE) incidence and changes in laboratory parameters. Platinum resistance status was obtained retrospectively, and responses to olaparib evaluated. RESULTS: In patients with gBRCA1/2m ovarian cancer, 154/193 (80%) had received ≥3 prior lines of chemotherapy, of whom 137/154 (89%) had measurable disease at baseline. ORR was 34% (46/137; 95% confidence interval [CI] 26-42) and median DoR was 7.9 (95% CI 5.6-9.6) months. ORR in platinum-resistant tumors was 30%. Median DoR for platinum-sensitive and platinum-resistant disease was similar: 8.2months (95% CI 5.6-13.5) compared with 8.0months (4.8-14.8), respectively. Six of the 193 (3%) patients had an AE with an outcome of death. None of these AEs at time of occurrence was considered causally related to olaparib. CONCLUSION: Following ≥3 prior lines of chemotherapy, olaparib 400mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified.


Subject(s)
Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Phthalazines/therapeutic use , Piperazines/therapeutic use , Aged , Antineoplastic Agents/therapeutic use , Drug Resistance, Neoplasm , Female , Humans , Middle Aged , Organoplatinum Compounds/pharmacology , Phthalazines/adverse effects , Piperazines/adverse effects , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Prospective Studies
4.
Curr Treat Options Cardiovasc Med ; 17(12): 60, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26490280

ABSTRACT

OPINION STATEMENT: Cardiovascular disease (CVD) and breast cancer cause substantial morbidity and mortality in women and are major public health concerns in the USA. While aggressive screening and targeted, advanced treatment for breast cancer have had a measurable impact on breast cancer survival, treatment is not without significant cardiotoxic effects. Anthracycline-based chemotherapy can lead to left ventricular dysfunction and failure, as well as a decline in exercise tolerance and cardio-pulmonary reserve despite preserved ejection fraction. Trastuzumab, a newer monoclonal antibody targeting the Her2 receptor used in the treatment of Her2+ cancer, is also linked to left ventricular dysfunction, although the long-term cardiac effects are presently unclear. Radiation treatment particularly for left-sided breast cancer has been associated with increased rates of ischemic heart disease. As women have increasing survival and cure rates from early breast cancer, long-term consequences on the heart that are secondary to therapy are a major concern. These need to be identified, treated, and avoided when possible. Further research and clear surveillance guidelines are needed to aid the practicing clinician in CVD prevention in breast cancer survivors.

5.
J Clin Oncol ; 33(3): 244-50, 2015 Jan 20.
Article in English | MEDLINE | ID: mdl-25366685

ABSTRACT

PURPOSE: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) -associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. PATIENTS AND METHODS: This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. RESULTS: A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease ≥ 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade ≥ 3 AEs were reported for 54% of patients; anemia was the most common (17%). CONCLUSION: Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations. Olaparib warrants further investigation in confirmatory studies.


Subject(s)
Antineoplastic Agents/therapeutic use , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Germ-Line Mutation , Neoplasms/drug therapy , Neoplasms/genetics , Phthalazines/therapeutic use , Piperazines/therapeutic use , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasms/pathology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Phthalazines/administration & dosage , Phthalazines/adverse effects , Piperazines/administration & dosage , Piperazines/adverse effects , Prospective Studies , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Treatment Outcome
6.
Pharmgenomics Pers Med ; 7: 307-16, 2014.
Article in English | MEDLINE | ID: mdl-25342917

ABSTRACT

Inhibitors of the poly(adenosine triphosphate-ribose) polymerase (PARP)-1 enzyme induce synthetic lethality in cancers with ineffective DNA (DNA) repair or homologous repair deficiency, and have shown promising clinical activity in cancers deficient in DNA repair due to germ-line mutation in BRCA1 and BRCA2. The majority of breast cancers arising in carriers of BRCA1 germ-line mutations, as well as half of those in BRCA2 carriers, are classified as triple-negative breast cancer (TNBC). TNBC is a biologically heterogeneous group of breast cancers characterized by the lack of immunohistochemical expression of the ER, PR, or HER2 proteins, and for which the current standard of care in systemic therapy is cytotoxic chemotherapy. Many "sporadic" cases of TNBC appear to have indicators of DNA repair dysfunction similar to those in BRCA-mutation carriers, suggesting the possible utility of PARP inhibitors in a subset of TNBC. Significant genetic heterogeneity has been observed within the TNBC cohort, creating challenges for interpretation of prior clinical trial data, and for the design of future clinical trials. Several PARP inhibitors are currently in clinical development in BRCA-mutated breast cancer. The use of PARP inhibitors in TNBC without BRCA mutation will require biomarkers that identify cancers with homologous repair deficiency in order to select patients likely to respond. Beyond mutations in the BRCA genes, dysfunction in other genes that interact with the homologous repair pathway may offer opportunities to induce synthetic lethality when combined with PARP inhibition.

7.
Invest New Drugs ; 31(5): 1345-54, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23801303

ABSTRACT

Hormone receptor-positive breast cancer is treated with estrogen inhibitors. Fulvestrant (FASLODEX™), an estrogen receptor (ER) antagonist with no known agonist effects, competitively binds, blocks and degrades the ER. Vascular endothelial growth factor (VEGF) may mediate resistance to ER antagonists. Cediranib is a highly potent VEGF signaling inhibitor with activity against all three VEGF receptors. This randomized Phase II study evaluated cediranib plus fulvestrant. Postmenopausal women with hormone-sensitive metastatic breast cancer were eligible. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response, clinical benefit rate (CBR), safety/tolerability and pharmacokinetics (PK). Patients received cediranib 45 mg/day (n=31) or placebo (n=31) both plus fulvestrant. Demographic/baseline characteristics were well balanced. Patients treated with cediranib had a numerical advantage in PFS (hazard ratio=0.867, P=0.669; median 223 vs. 112 days, respectively) and ORR (22 vs. 8 %, respectively) vs. placebo, although not statistically significant. CBR was 42 % in both arms. The most common adverse events (AEs) in the cediranib arm were diarrhea (68 %), fatigue (61 %) and hypertension (55 %). The incidence of grade ≥ 3 AEs (68 % vs. 32 %), serious AEs (48 % vs. 13 %), discontinuation AEs (39 % vs. 10 %), and cediranib dose reductions/interruptions (74 % vs. 32 %) were higher in the cediranib arm. There was no evidence of a clinically relevant effect of cediranib on fulvestrant PK. Cediranib plus fulvestrant may demonstrate clinical activity in this population, but cediranib 45 mg was not sufficiently well tolerated. Investigation of lower doses of cediranib plus hormonal/chemotherapy could be considered.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Adolescent , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Breast Neoplasms/blood , Breast Neoplasms/pathology , Estradiol/administration & dosage , Estradiol/adverse effects , Estradiol/analogs & derivatives , Estradiol/pharmacokinetics , Estrogen Antagonists/administration & dosage , Estrogen Antagonists/adverse effects , Estrogen Antagonists/pharmacokinetics , Female , Fibroblast Growth Factor 2/blood , Fulvestrant , Humans , Middle Aged , Neoplasm Metastasis , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacokinetics , Quinazolines/administration & dosage , Quinazolines/adverse effects , Quinazolines/pharmacokinetics , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor Receptor-2/blood , Young Adult
9.
Lancet ; 376(9737): 235-44, 2010 Jul 24.
Article in English | MEDLINE | ID: mdl-20609467

ABSTRACT

BACKGROUND: Olaparib, a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor, induced synthetic lethality in BRCA-deficient cells. A maximum tolerated dose and initial signal of efficacy in BRCA-deficient ovarian cancers have been reported. We therefore assessed the efficacy, safety, and tolerability of olaparib alone in women with BRCA1 or BRCA2 mutations and advanced breast cancer. METHODS: Women (aged >or=18 years) with confirmed BRCA1 or BRCA2 mutations and recurrent, advanced breast cancer were assigned to two sequential cohorts in a phase 2 study undertaken in 16 centres in Australia, Germany, Spain, Sweden, the UK, and the USA. The first cohort (n=27) was given continuous oral olaparib at the maximum tolerated dose (400 mg twice daily), and the second (n=27) was given a lower dose (100 mg twice daily). The primary efficacy endpoint was objective response rate (ORR). This study is registered with ClinicalTrials.gov, number NCT00494234. FINDINGS: Patients had been given a median of three previous chemotherapy regimens (range 1-5 in cohort 1, and 2-4 in cohort 2). ORR was 11 (41%) of 27 patients (95% CI 25-59) in the cohort assigned to 400 mg twice daily, and six (22%) of 27 (11-41) in the cohort assigned to 100 mg twice daily. Toxicities were mainly at low grades. The most frequent causally related adverse events in the cohort given 400 mg twice daily were fatigue (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), nausea (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), vomiting (grade 1 or 2, three [11%]; grade 3 or 4, three [11%]), and anaemia (grade 1 or 2, one [4%]; grade 3 or 4, three [11%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, 11 [41%]; none grade 3 or 4) and fatigue (grade 1 or 2, seven [26%]; grade 3 or 4, one [4%]). INTERPRETATION: The results of this study provide positive proof of concept for PARP inhibition in BRCA-deficient breast cancers and shows a favourable therapeutic index for a novel targeted treatment strategy in patients with tumours that have genetic loss of function of BRCA1-associated or BRCA2-associated DNA repair. Toxicity in women with BRCA1 and BRCA2 mutations was similar to that reported previously in those without such mutations. FUNDING: AstraZeneca.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Phthalazines/therapeutic use , Piperazines/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors , Adult , Aged , Breast Neoplasms/pathology , Female , Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Humans , Maximum Tolerated Dose , Middle Aged , Prospective Studies
10.
Lancet ; 376(9737): 245-51, 2010 Jul 24.
Article in English | MEDLINE | ID: mdl-20609468

ABSTRACT

BACKGROUND: Olaparib is a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. We aimed to assess the efficacy and safety of olaparib for treatment of advanced ovarian cancer in patients with BRCA1 or BRCA2 mutations. METHODS: In this international, multicentre, phase 2 study, we enrolled two sequential cohorts of women (aged >or=18 years) with confirmed genetic BRCA1 or BRCA2 mutations, and recurrent, measurable disease. The study was undertaken in 12 centres in Australia, Germany, Spain, Sweden, and the USA. The first cohort (n=33) was given continuous oral olaparib at the maximum tolerated dose of 400 mg twice daily, and the second cohort (n=24) was given continuous oral olaparib at 100 mg twice daily. The primary efficacy endpoint was objective response rate (ORR). This study is registered with ClinicalTrials.gov, number NCT00494442. FINDINGS: Patients had been given a median of three (range 1-16) previous chemotherapy regimens. ORR was 11 (33%) of 33 patients (95% CI 20-51) in the cohort assigned to olaparib 400 mg twice daily, and three (13%) of 24 (4-31) in the cohort assigned to 100 mg twice daily. In patients given olaparib 400 mg twice daily, the most frequent causally related adverse events were nausea (grade 1 or 2, 14 [42%]; grade 3 or 4, two [6%]), fatigue (grade 1 or 2, ten [30%]; grade 3 or 4, one [3%]), and anaemia (grade 1 or two, five [15%]; grade 3 or 4, one [3%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, seven [29%]; grade 3 or 4, two [8%]) and fatigue (grade 1 or 2, nine [38%]; none grade 3 or 4). INTERPRETATION: Findings from this phase 2 study provide positive proof of concept of the efficacy and tolerability of genetically targeted treatment with olaparib in BRCA-mutated advanced ovarian cancer. FUNDING: AstraZeneca.


Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Phthalazines/therapeutic use , Piperazines/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors , Adult , Aged , Female , Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Humans , Maximum Tolerated Dose , Middle Aged , Ovarian Neoplasms/pathology , Prospective Studies
11.
N Engl J Med ; 358(20): 2184-5; author reply 2185, 2008 May 15.
Article in English | MEDLINE | ID: mdl-18494080
13.
Nucleic Acids Res ; 27(2): 649-55, 1999 Jan 15.
Article in English | MEDLINE | ID: mdl-9862993

ABSTRACT

A flexible chemistry for solid phase attachment of oligonucleotides is described. Oligonucleotides bearing 5'-terminal acrylamide modifications efficiently co-polymerize with acrylamide monomers to form thermally stable DNA-containing polyacrylamide co-polymers. Co-polymerization attachment is specific for the terminal acrylamide group. Stable probe-containing layers are easily fabricated on supports bearing exposed acrylic groups, including plastic microtiter plates and silanized glass. Attachment can be accomplished using standard polyacrylamide gel recipes and polymerization techniques. Supports having a high surface density of hybridizable oligonucleotide (approximately 200 fmol/mm2) can be produced.


Subject(s)
Acrylamides/chemistry , Oligonucleotide Array Sequence Analysis , Oligonucleotides/chemistry , Acrylic Resins , Glass , Polymerase Chain Reaction , Polymers , Polystyrenes
16.
Am J Clin Oncol ; 13(4): 324-6, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2198795

ABSTRACT

Carbetimer (carboxyimamidate) was administered at a dose of 6,500 mg/m2/day intravenously for 5 consecutive days to 14 patients with measurable metastatic or recurrent colorectal cancer in a single institution phase II study of the Northern California Oncology Group. A total of 38 cycles of therapy were administered; nine patients completed at least three cycles of treatment. No partial or complete responses were observed. One patient did have a greater than 50% response in the liver while developing new retroperitoneal lymphadenopathy and is considered a nonresponder. Carbetimer was well tolerated with elevations of calcium from 10.2 to 12.5 mg/dl in nine patients, prolongation of prothrombin time and partial thromboplastin time in 14 patients, proteinuria in 10 patients, dizziness in six patients, nausea in two patients, and venous pain during infusion in three patients. Myelosuppression was not observed. Carbetimer at this dose and schedule is inactive in the treatment of colorectal cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Polymers/therapeutic use , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/toxicity , Calcium/blood , Drug Evaluation , Female , Humans , Hypercalcemia/chemically induced , Male , Middle Aged , Multicenter Studies as Topic , Polymers/administration & dosage , Polymers/toxicity , Remission Induction
17.
Cancer ; 61(9): 1782-6, 1988 May 01.
Article in English | MEDLINE | ID: mdl-3355976

ABSTRACT

Four cases of plasmacytoma (PC), six cases of multiple myeloma (MM), and nine cases of immunoblastic lymphoma (IL) of B-cell phenotype were studied with a large panel of monoclonal antibodies applied to frozen tissue sections. There were no significant differences in the immunophenotypes of plasmacytomas and multiple myelomas. However, significant immunophenotypic differences were noticed between the plasmacytoma/multiple myeloma cases (PC/MM) and the immunoblastic lymphoma specimens. The PC/MM cases characteristically stained with alpha (or gamma) and T10 and did not usually stain with mu, leukocyte common antibodies, certain B-lineage antibodies (B1, T015, 4G7, 6A4), or Ia. In contrast, IL sections usually did not stain with alpha or T10 and generally did stain with mu (or gamma), leukocyte common antibodies, B-lineage antibodies, and Ia. Ki-67, an antibody to proliferating cells, stained significantly fewer cells in PC/MM than in IL and stained significantly fewer cells that had a good clinical outcome. We conclude that although no one antibody is useful in distinguishing PC/MM from IL, the application of a panel of antibodies may be helpful in making this distinction. The prognosis may correlate with the numbers of proliferating cells as measured by reactivity with Ki-67.


Subject(s)
Antibodies, Monoclonal/immunology , Lymphoma, Non-Hodgkin/immunology , Multiple Myeloma/immunology , Plasmacytoma/immunology , Antigens, Neoplasm/analysis , Humans , Lymphoma, Non-Hodgkin/pathology , Multiple Myeloma/pathology , Neoplasm Proteins/analysis , Phenotype , Plasmacytoma/pathology , Prognosis
18.
J Am Geriatr Soc ; 30(5): 299-302, 1982 May.
Article in English | MEDLINE | ID: mdl-6281325

ABSTRACT

Twenty-four patients over the age of 70 with small cell cancer of the lung were studied retrospectively. Ninety-two per cent of these patients had other concurrent medical disorders; 58 per cent had cardiac disease and 25 per cent had a second malignancy. The median survival of 20 treated patients was ten months, and the one-year survival was 30 per cent. Such elderly patients with multiple medical problems can benefit from combination chemotherapy.


Subject(s)
Carcinoma, Small Cell/drug therapy , Lung Neoplasms/complications , Aged , Carcinoma, Small Cell/complications , Drug Therapy, Combination , Female , Heart Diseases/complications , Humans , Lung Diseases, Obstructive/complications , Lung Neoplasms/drug therapy , Male , Neoplasms, Multiple Primary , Retrospective Studies
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