scholarly journals 873. A Retrospective Cohort Study on Treatment Outcomes of Patients on Third-Line Therapy at the HIV Advanced Treatment Centre, University Teaching Hospital, Zambia

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S528-S528
Author(s):  
Mona-Gekanju Toeque ◽  
Brianna Lindsay ◽  
Paul Msanzya Zulu ◽  
Sombo Fwoloshi ◽  
Duncan Chanda ◽  
...  
Keyword(s):  
Viral Load ◽  
Teaching Hospital ◽  
Resistance Mutation ◽  
University Teaching ◽  
Virologic Suppression ◽  
Immunologic Response ◽  
Second Line ◽  
Line Therapy ◽  
Third Line

Abstract Background In Zambia, third-line regimens consist of a switch to darunavir/ritonavir (DRV/r) and/or raltegravir (RAL) and/or etravirine (ETV), and as of 2017, dolutegravir (DTG), from a failing second-line therapy.5 We assessed virologic suppression (HIV viral load (VL) ≤1000 copies/ml per Zambian national guidelines), immunological response, and patterns of HIV drug resistance mutation among patients on third-line ART at the University Teaching Hospital (UTH) in Lusaka, Zambia. Methods A retrospective evaluation of adults ≥18 years old on third-line ART regimens at UTH between January 2012 to June 30, 2020 was conducted. Patients were referred for second-line virologic failure defined as HIV RNA VL > 1000 copies/mL on two consecutive measurements after 6 months on second-line ART.5 We assessed virologic suppression VL ≤1000 copies/ml, CD4, mutations, and third-line regimens of this cohort. Patients were excluded if they were on third-line ART < 6 months or received RAL and/or ETV and/or DTG before starting third-line ART. Results A total of 539 patients were included; 231 males (42.9%) and 308 (57.1%) females. The mean age of third-line initiation was 29.8 years; mean time from ART initiation to third-line initiation was 9.9 years. Out of 25 combination 349 (64.7%) received DTG, 272 (50.5%) DRV/r, 85(15.8%) ETR, and 49 (9.1%) RAL. There were 215 (39.9%) genotypes; common mutations were to zidovudine (80%), non-nucleoside reverse transcriptase inhibitors (NNRTIs) (78%), and protease inhibitors (PIs) (41%). Patients with at least one viral load and CD4 upon third-line initiation was 296 (54.9%) and 350 (64.9%), respectively. Among patients with sufficient data (21%, n=115), VL suppression increased from 44 (38%) patients at baseline to 53 (46%) at next available follow-up; with mean baseline VL and follow-up VL of log10 3.60 and 3.33, respectively. The immunologic response revealed 49 (56.3%) had CD4 increase with mean increase of 61.1 cells/mm3. (See Table 1.) Conclusion We found moderate improvements in VL suppression and immunologic response. Nearly all third-line patients had genotypic resistance to first-line NNRTI and nearly half to second-line PI regimens. Quality improvement measures are needed to improve viral load timing following ART changes to better assess regimen efficacy. Disclosures All Authors: No reported disclosures

Outcome of Patients with CML Treated with Dasatinib or Nilotinib after Failure of Second Prior TKIs

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2294-2294
Author(s):  
Antonella Russo Rossi ◽  
Massimo Breccia ◽  
Fausto Castagnetti ◽  
Luigiana Luciano ◽  
Antonella Gozzini ◽  
...  
Keyword(s):  
Median Time ◽  
Conflicts Of Interest ◽  
Cell Uptake ◽  
Second Line ◽  
The Third ◽  
Line Therapy ◽  
Third Line ◽  
New Mutations

Abstract Abstract 2294 Background. The TKIs Nilotinib and Dasatinib offer additional therapeutic options for patients with CML who are resistant or intolerant to Imatinib. These agents, active against the majority of Imatinib resistant BCR-ABL mutated clones, have a different pattern of kinase target selectivity, pharmacokinetics parameters, cell uptake, efflux properties and adverse events profiles. Preliminary results suggest that some patients may respond to a second TKI used as third line therapy, but little is known about the long term benefit of such an approach.Aim of this collaborative Italian study was to verify the response (rate and duration) and the clinical outcome in patients with CML treated with a third TKI after sequential failure of the previous ones. Methods. We evaluated 66 patients with CML, resistant/intolerant to Imatinib and treated with Dasatinib or Nilotinib, then switched to a third- line TKI after treatment failure. Of these, 29 patients were treated with dasatinib after imatinib/nilotinib failure and 37 with nilotinib after imatinib/dasatinib failure. Patients were monitored with complete blood counts, cytogenetic analysis, bone marrow aspiration RT-PCR and mutational analysis. Results. A total of 66 patients (median age 63 years, range, 33–85 years) were treated with sequential TKIs; 40 (61%) patients had received interferon-a before starting Imatinib; 26 (39%) patients received imatinib as first line therapy. The median time on imatinib therapy was 47.5 months (range 4–101 months). At the start of nilotinib as second line, 27/29 (93%) patients were in CP, 1 (3.5%) in AP, and 1 (3.5%) in BP. 9 patients (31%) had developed mutations before starting treatment. The median time on second line TKI was 8 months (range 2–36 months). In the resistant patients 4 new mutations were identified (F359V in two patients, T315I, Y253H+F359V). At the start of dasatinib as second line, 33/37 (89.2%) patients were in CP, 4 (10.8%) in AP. 7 patients (18.9%) had developed mutations before starting treatment. The median time on second line TKI was 14 months (range 4–59 months).In the resistant patients 5 new mutations were identified (F137L in three pts, M318T, M244V+F317L). At the start of the third TKI, 60/66 (90.9%) patients were in CP, 5 (7.6%) in AP, and 1 (1.5%) in BP. Of these, 7 patients (18.9%) on dasatinib and 7 (24.1%) on nilotinib had mutations before starting treatment. The best response to the third line treatment with TKI was 10 (15.2%) MMR, 10 (15.2%) CCyR, 8 PcyR (12.1%), 5 (7.5%) mCyR, 24 (36.4%) CHR and 9 (13.6%) No Response (NR). In the dasatinib group, 9 (31%) patients discontinued treatment because of toxicity versus 17 (45.9%) patients in the nilotinib group.Two new mutations (F317L, E255V) emerged with dasatinib as third line therapy.After a median follow up of 13 months (range 2–37 months) 50 patients (48 CP, 2 AP) are continuing therapy (33 on nilotinib, 17 on dasatinib).Since the start of the third TKI, 61 patients (92.4%) are still alive for a median overall survival of 110 months (range 15–300) (52 CP, 7 AP, 2 NA); the 5 deaths (7.6%) were caused by disease progression and spread of the gene mutation T315I. Discussion. In our study, about one third of patients derived benefit from the use of three sequential TKIs; patients with better, longer response (28.7%) to third TKI were the same patients with a better response to the Imatinib and 2TKIs therapy. All these patients had taken interferon therapy before the Imatinib. In this subset of patients (good responders: CCyR and MMR) 5 patients developed mutations that were sensitive to the sequential treatment.The lack of a durable cytogenetic remission could be explained by the emergence of new kinase domain mutations as patients are exposed to sequential TKI; a change of therapy resulted in an adequate response. In our series, patients with poor prognosis showed mutations not sensitive to the TKIs treatment. Conclusions. Although allogeneic SCT is the treatment of choice in all patients failing 2 TKIs who are suitable candidates for this approach, alternative strategies are required for ineligible patients. The use of a third TKI after failure of two previous TKIs induces response in some patients. Longer follow up of a larger series of patients is needed to determine the long term impact of the response. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5880-5880
Author(s):  
Nathan H Fowler ◽  
Yanni Hao ◽  
Stephen Lim ◽  
Guifang Chen ◽  
Frank Li ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line ◽  
Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

scholarly journals Viral load care of HIV-1 infected children and adolescents: A longitudinal study in rural Zimbabwe

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245085
Author(s):  
Tichaona Mapangisana ◽  
Rhoderick Machekano ◽  
Vinie Kouamou ◽  
Caroline Maposhere ◽  
Kathy McCarty ◽  
...  
Keyword(s):  
Viral Load ◽  
Children And Adolescents ◽  
Virologic Failure ◽  
Sub Saharan Africa ◽  
Virologic Suppression ◽  
Second Line ◽  
Load Testing ◽  
Viral Load Suppression ◽  
Viral Load Testing

Introduction Maintaining virologic suppression of children and adolescents on ART in rural communities in sub-Saharan Africa is challenging. We explored switching drug regimens to protease inhibitor (PI) based treatment and reducing nevirapine and zidovudine use in a differentiated community service delivery model in rural Zimbabwe. Methods From 2016 through 2018, we followed 306 children and adolescents on ART in Hurungwe, Zimbabwe at Chidamoyo Christian Hospital, which provides compact ART regimens at 8 dispersed rural community outreach sites. Viral load testing was performed (2016) by Roche and at follow-up (2018) by a point of care viral load assay. Virologic failure was defined as viral load ≥1,000 copies/ml. A logistic regression model which included demographics, treatment regimens and caregiver’s characteristics was used to assess risks for virologic failure and loss to follow-up (LTFU). Results At baseline in 2016, 296 of 306 children and adolescents (97%) were on first-line ART, and only 10 were receiving a PI-based regimen. The median age was 12 years (IQR 8–15) and 55% were female. Two hundred and nine (68%) had viral load suppression (<1,000 copies/ml) and 97(32%) were unsuppressed (viral load ≥1000). At follow-up in 2018, 42/306 (14%) were either transferred 23 (7%) or LTFU 17 (6%) and 2 had died. In 2018, of the 264 retained in care, 107/264 (41%), had been switched to second-line, ritonavir-boosted PI with abacavir as a new nucleotide analog reverse transcriptase inhibitor (NRTI). Overall viral load suppression increased from 68% in 2016 to 81% in 2018 (P<0.001). Conclusion Viral load testing, and switching to second-line, ritonavir-boosted PI with abacavir significantly increased virologic suppression among HIV-infected children and adolescents in rural Zimbabwe.

Efficacy of Tyrosine Kinase Inhibitors (TKIs) as Third Line Therapy In Patients with Chronic Myeloid Leukaemia In Chronic Phase Who Have Failed Two Prior TKIs

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2274-2274
Author(s):  
Amr R Ibrahim ◽  
Marco Bua ◽  
Jamshid S Khorshad ◽  
Dragana Milojkovic ◽  
Lina Eliasson ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Cytogenetic Response ◽  
Second Line ◽  
Second Line Therapy ◽  
The Third ◽  
Line Therapy ◽  
History Of ◽  
Third Line Therapy ◽  
Third Line

Abstract Abstract 2274 Patients with CML in chronic phase who have failed imatinib therapy are commonly treated with dasatinib or nilotinib, but a significant proportion fail to respond or relapse in which case they are often treated with the other tyrosine kinase inhibitor (TKI) that they had not yet received. We report here the largest series of CML patients in CP treated with a third line TKI after failing both imatinib and another TKI. We enrolled 26 patients. The median age was 64 years and 54% were male. 20 patients had received dasatinib and 6 nilotinib as second line therapy. All patients were still in first CP at the moment of commencing third line therapy, and none was harboring a T315I mutation. Failure to second line therapy was defined as no CHR at 3 months, no major cytogenetic response (MCyR) at 12 months or loss of a hematological or cytogenetic response. Patients who were unable to continue therapy on account of toxicity were also considered as having failed therapy. The median follow up for the surviving patients after starting third line therapy was 21.5 months (range, 6 – 46.5 months). The 2.5 years (30 months) cumulative incidences of MCyR, CCyR and MMR were 48.2%, 32.4%, 21.1% respectively. Multivariate analysis showed that the achievement of at least MiCyR (<95% Ph-positive) on imatinib (RR=5.6, p=0.03) or on second line therapy (RR=11.8, p=0.006) were the only independent predictors for the achievement of CCyR. When combining both variables we found that patients who had achieved MiCyR on one of the two prior therapies had a significantly better OS and higher probability of achieving cytogenetic response on third line therapy, i.e. the 30 month probability of OS and CCyR were 72.7% vs 20.4% (p=0.03) and of 71.4% vs 0% (p=0.0005) respectively (Figure). During follow up 9 (34.6%) patients died. The probability of OS at 30 months was 46.7%. The achievement of a cytogenetic response on second line and age younger than 64 (possibly reflecting eligibility for transplantation) were the only independent predictors for OS (RR=6.5, p=0.02 and RR=0.13, p= 0.02). Seventeen patients (65%) were classified as intolerant to previous therapies (imatinib or second line TKI). Intolerant patients had a probability of responding to the third line therapy similar to those of the resistant patients, but when this cohort was subdivided according to the type of intolerance we found that 11 patients who had hematologic toxicity with either therapy had a probability of CCyR at 30 months lower than that of the remaining 15 patients (11.1% vs 47.5 %, p=0.03), while the 8 patients with non-hematologic intolerance to the imatinib or to the second line had a probability of 30-month CCyR greater than that of the remaining 18 patients (87.5% vs 5.6%, p<0.001). At 3 months 26 patients remained on follow up, of whom 9 patients had achieved at least MiCyR. These 9 patients had better 30-month probabilities of CCyR and OS than the patients who had failed to achieve MiCyR, namely 88.9% vs 13.3% (p<0.0001), and 87.5% vs. 35.0% (p=0.1). When we excluded the only patient who died of non-leukemia related causes while in CCyR, the probabilities of OS was 100% vs 35.0% (p=0.04) Which patients should be offered third line TKI therapy? Patients who achieved cytogenetic response on first or second line therapy and patients with a history of non-hematologic intolerance to the prior TKI benefited from a third TKI. Patients with primary cytogenetic resistance to two TKIs or with a history of hematologic intolerance should receive an allogeneic stem cell transplant when possible. For patients in this situation who lack a transplant option we would recommend only a short course (3 months) of the third line therapy to identify responders. Non-responders should be offered experimental studies. Disclosures: Marin: Bristol-Myers Squibb: Consultancy; Novartis: Consultancy, Research Funding.

scholarly journals Aphakia Correction by Injection of Foldable Intra Ocular Lens in the Anterior Chamber

2013 ◽  
Vol 5 ◽  
pp. OED.S12672
Author(s):  
Kagmeni Giles ◽  
Moukouri Ernest ◽  
Domngang Christelle ◽  
Nguefack-Tsague Georges ◽  
Cheuteu Raoul ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Intraocular Pressure ◽  
Anterior Chamber ◽  
Teaching Hospital ◽  
Case Series ◽  
University Teaching ◽  
Case Series Study ◽  
The Mean ◽  
The University

We assessed the outcomes of the use of anterior chamber foldable lens for unilateral aphakia correction at the University Teaching Hospital of Yaounde. In this retrospective, non-comparative, consecutive case series study, we reviewed the records of patients who underwent an operation for aphakia correction by the means of injection of an angular supported foldable lens between January 2009 and December 2011 in the University Teaching Hospital Yaounde. Student's paired t-test was carried out to compare preoperative and postoperative visual acuity (VA) and intraocular pressure (TOP). P-values less than 0.05 were considered statistically significant. Twenty-one patients were included in the study; twelve were male (57.1%) and nine were female (42.9%). The mean age was 55.38 ± 17.67 years (range 9–75 years). The mean follow-up duration was 5.95 ± 3.14 months (range 2–12 months). The mean logMAR visual acuity was 1.26 ± 0.46 pre-operatively and 0.78 ± 0.57 post-operatively ( P = 0.003). The change in intraocular pressure was not statistically significant. Complications included intraocular hypertension (over 21 mmHg) in 3 patients (14.3%) and macular edema, pupillar ovalization, and retinal detachment in one patient each. The results indicate that injection of an angular support foldable lens in the anterior chamber is a useful technique for the correction of aphakia in eyes without capsular support. More extended follow-up, however, and a larger series of patients are needed to ascertain the effectiveness and safety of this procedure.

Characteristics, treatment patterns, and economic burden of patients with metastatic cervical cancer receiving systemic anticancer therapy.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 51-51
Author(s):  
Xiaoyun Pan ◽  
Lincy S. Lal ◽  
John White ◽  
Seyed Hamidreza Mahmoudpour ◽  
Christian Valencia
Keyword(s):  
Cervical Cancer ◽  
Economic Burden ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Duration Of Treatment ◽  
Second Line Therapy ◽  
Treatment Regimens ◽  
Line Therapy

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]

Investigation of aStreptococcus viridansPseudobacteremia Epidemic at a University Teaching Hospital

1989 ◽  
Vol 10 (9) ◽  
pp. 416-421 ◽  
Author(s):  
Deirdre L. Church ◽  
Heather E. Bryant
Keyword(s):  
Blood Culture ◽  
Teaching Hospital ◽  
Index Finger ◽  
Blood Cultures ◽  
University Teaching ◽  
Large Teaching Hospital ◽  
Disproportionate Number ◽  
Good Concordance ◽  
Contaminated Blood

AbstractFor several months in 1986, an outbreak of Streptococcus viridanspseudobacteremia occurred at a large teaching hospital. All sources of laboratory blood culture contamination were excluded. A retrospective epidemiological study indicated that one phlebotomist, “P,” collected a disproportionate number of the positive blood cultures. Further comparison of the paired blood culture results from the three months when the incidence was highest revealed a good concordance of results among all other phlebotomists (Kappa = 0.5), while P's results concurred with others less frequently than would be expected even by chance (Kappa < 0.0). Clinical follow-up showed that P did not routinely wear gloves while drawing blood and had eczema of the hands. Skin scrapings from the hands, right index finger/fingernail grew predominantlyS viridansspecies that were compatible with those recovered from contaminated blood cultures. This epidemic demonstrated the need for early detection of this source as a cause of nosocomial pseudobacteremia.

Clinical Evidence for Topotecan-Paclitaxel Non–Cross-Resistance in Ovarian Cancer

2001 ◽  
Vol 19 (7) ◽  
pp. 1893-1900 ◽  
Author(s):  
Martin Gore ◽  
Wim ten Bokkel Huinink ◽  
James Carmichael ◽  
Alan Gordon ◽  
Neville Davidson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Response Rates ◽  
Cross Resistance ◽  
Second Line ◽  
Similar Activity ◽  
Line Therapy ◽  
Number Of Patients ◽  
Alternative Drug ◽  
Third Line Therapy ◽  
Third Line

PURPOSE: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non–cross-resistance between these two compounds. PATIENTS AND METHODS: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m2/d) × 5 every 21 days (n = 112) or paclitaxel (175 mg/m2 over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. RESULTS: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P = .638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). CONCLUSION: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non–cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.

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