Tracking symptoms related to treatment toxicity is standard practice in routine care and during clinical trials. Currently, clinicians collect symptom information via complex and often inefficient ...mechanisms, but there is growing interest in collecting outcome information directly from patients.
The National Cancer Institute Common Terminology Criteria for Adverse Events schema for seven common symptoms was adapted into a Web-based patient-reporting system, accessible from desktop computers in outpatient clinics and from home computers. Eighty patients with gynecologic malignancies beginning standard chemotherapy regimens were enrolled between April and September 2004. During an 8-week observation period, participants were encouraged to log in and report symptoms at each follow-up visit, or alternatively, to access the system from home.
All patients completed an initial log in. At each subsequent appointment, most enrollees (80% to 85%) reported symptoms using the online system, with a mean of three follow-up visits per patient during the observation period (range, one to six). Sixty of 80 patients (75%) logged in at least once from home. Use was significantly associated with prior Internet experience. Forty-two severe toxicities (grade 3 to 4) entered from home prompted seven clinician interventions. Most patients (96%) found the system useful and would recommend it to others.
Patients are capable of reporting symptoms experienced during chemotherapy using a Web-based interface. Assessment in the clinical trial setting and comparison of direct patient- versus clinician-based approaches for reporting symptoms and their severity are warranted.
We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer.
This was a ...single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1–3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013–7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS6) and overall response rate (ORR) by RECIST 1.1 criteria.
During the study period, 160 patients were screened and 59 (45 high-grade serous HGS and 14 low-grade serous LGS) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2–100%). The overall PFS6 rate (as binary) was 22% (90% CI: 15.1–100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7–100%) and 38.5% (90% CI: 21.7%–100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug.
The study met its primary endpoint, with a PFS6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients.
•Enzalutamide was well-tolerated in AR+ recurrent ovarian cancer patients and demonstrated a suitable safety profile.•This study met its primary endpoint, as enzalutamide afforded modest progression-free survival.•The overall response rate to enzalutamide was low, with less than 2% of patients demonstrating radiographic response.•Further study of enzalutamide may be warranted, particularly in patients with AR+ low-grade serous ovarian cancer.
Few chemotherapy agents are active in leiomyosarcoma (LMS), particularly LMS that has progressed after doxorubicin treatment. We sought to determine the response to gemcitabine plus docetaxel among ...patients with LMS.
Patients with unresectable LMS of uterine (n = 29) or other (n = 5) primary sites who did not respond to zero to two prior chemotherapy regimens were enrolled onto a phase II study of gemcitabine 900 mg/m(2) intravenously (i.v.) on days 1 and 8 plus docetaxel 100 mg/m(2) i.v. on day 8 with granulocyte colony-stimulating factor given subcutaneously on days 9 to 15, delivered every 21 days. Patients with prior pelvic radiation received 25% lower doses of both agents. Gemcitabine was delivered over 30 or 90 minutes in cycles 1 and 2 and by 90-minute infusion in all subsequent cycles. Pharmacokinetic studies assessed in vivo differences in gemcitabine concentrations with different rates of infusion.
Thirty-four patients (median age, 55 years; range, 32 to 74 years) have enrolled. Fourteen had received prior pelvic radiation. Sixteen of 34 patients had progressed after doxorubicin-based therapy; 18 had no prior chemotherapy. Among 34 patients, complete response was observed in three patients and partial response in 15, for an overall response rate of 53% (95% confidence interval, 35% to 70%). Seven patients had stable disease. Fifty percent of patients previously treated with doxorubicin responded. Hematologic toxicity was common (neutropenia: grade 3, 15%; grade 4, 6%; thrombocytopenia: grade 3, 26%; grade 4, 3%), but neutropenic fever (6%) and bleeding events (0%) were rare. The median time to progression was 5.6 months (range, 4 to 10 months).
Gemcitabine plus docetaxel is tolerable and highly active in treated and untreated patients with LMS.
To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal ...cancer in second or greater complete clinical remission.
Eleven patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were administered at weeks 1, 2, 3, 7, and 15. Periodic blood and urine samples were obtained to monitor safety (complete blood count, comprehensive panel, amylase, thyroid-stimulating hormone, and urinalysis) and antibody production (ELISA, fluorescence-activated cell sorting, and complement-dependent cytotoxicity).
Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2 in two patients), fever, myalgia, and localized injection site reactions were most frequent. No clinically relevant hematologic abnormalities were noted. No clinical or laboratory evidence of autoimmunity was seen. Serologic responses by ELISA were largely IgM against each antigen with the exception of Tn-MUC1 where both IgM and IgG responses were induced. Antibody responses were generally undetectable before immunization. After immunization, median IgM titers were as follows: Tn-MUC1, 1:640 (IgG 1:80); Tn, 1:160; TF, 1:640; Globo-H, 1:40; and STn, 1:80. Only one response was seen against Lewis Y; two were against GM2. Eight of nine patients developed responses against at least three antigens. Antibody titers peaked at weeks 4 to 8 in all patients. Fluorescence-activated cell sorting and complement-dependent cytotoxicity analysis showed substantially increased reactivity against MCF7 cells in seven of nine patients, with some increase seen in all patients.
This heptavalent-KLH conjugate plus QS21 vaccine safely induced antibody responses against five of seven antigens. Investigation in an adequately powered efficacy trial is warranted.
We assessed the safety and maximum tolerated dose (MTD) of the poly ADP-ribose polymerase (PARP) inhibitor olaparib with intravenous (IV)/intraperitoneal (IP) cisplatin/paclitaxel and IV bevacizumab, ...followed by olaparib and bevacizumab maintenance, in patients with newly diagnosed ovarian cancer who had undergone primary debulking surgery.
Treatment included: (Cycles 1–6) Day 1, IV paclitaxel 135 mg/m2/3 h + (from Cycle 2 onward) bevacizumab 15 mg/kg; Day 2, IP cisplatin 75 mg/m2; Days 2–8, olaparib (50/100/200 mg BID); Day 8, IP paclitaxel 60 mg/m2 of a 21-day cycle. Maintenance (Cycles 7–22) included: olaparib 300 mg BID and bevacizumab 15 mg/kg Day 1. The primary endpoint was MTD of olaparib, chemotherapy, and bevacizumab.
Seventeen women were treated (Cohort 1 50 mg olaparib, 8 patients; Cohort 2 100 mg, 3 patients; and Cohort 3 200 mg, 6 patients). Median age was 57 years (47–73); 94% had stage III disease; 29% had a germline BRCA mutation. Two of 6 patients in Cohort 3 experienced a dose-limiting toxicity (DLT). Grade 3/4 toxicities included: neutropenia (56%), lymphopenia (31%), anemia (25%), and fatigue (19%). Most patients started (88%, 81%) and completed (75%, 50%) maintenance olaparib and bevacizumab, respectively; 36% of patients on olaparib maintenance required a dose reduction. Median PFS was 33 months (26.2-NA).
The MTD of intermittently dosed olaparib with concurrent IV/IP cisplatin/paclitaxel and bevacizumab is 100 mg BID. Non-hematologic toxicities were predominantly low grade. One-third of patients on olaparib maintenance required dose reduction.
•The optimal upfront chemo and maintenance therapy for advanced ovarian cancer patients is rapidly evolving.•The role of intravenous (IV)/intraperitoneal (IP) chemotherapy remains unclear.•Phase I study of IV/IP cisplatin, paclitaxel, concurrent olaparib and bevacizumab with olaparib and bevacizumab maintenance•The maximum tolerated dose of olaparib with concurrent IV/IP cisplatin, paclitaxel and IV bevacizumab is 100 mg twice daily.•One third of patients required a dose reduction of maintenance olaparib.
The clinical course of ovarian cancer is often marked by periods of relapse and remission until chemotherapy resistance develops. Patients in remission with minimal disease burdens are ideally suited ...for the evaluation of immune-based strategies. The role of immune surveillance in improving outcome has been supported by the correlation of increased survival with the presence or absence of tumor-infiltrating lymphocytes in a given patient. Major obstacles to the development of successful immune strategies include the identification of tumor-restricted immunogenic targets, generation of a sufficient immune response to cause tumor rejection, and approaches to overcome evasion of immune attack. As optimal strategies are being developed, many questions remain. Some of the questions are as follows: What is the best antigen form (eg, peptides, proteins, or tumor lysates)? What are the appropriate adjuvants? Are monovalent or multivalent vaccines likely to be more effective? What is the optimal frequency and duration of vaccination? How should antigen-specific responses be monitored? How should the anticancer response be maintained? In this review, we will explore representative examples of immune strategies under investigation for patients with ovarian carcinoma that illustrate many of these issues. We will review ongoing phase III studies for patients in first clinical remission. Basic principles generic to all these immunotherapeutic approaches will be discussed in the hopes of yielding the most promising results as the field continues to evolve.
Cancer classification is foundational for patient care and oncology research. Systems such as International Classification of Diseases for Oncology (ICD-O), Systematized Nomenclature of Medicine ...Clinical Terms (SNOMED-CT), and National Cancer Institute Thesaurus (NCIt) provide large sets of cancer classification terminologies but they lack a dynamic modernized cancer classification platform that addresses the fast-evolving needs in clinical reporting of genomic sequencing results and associated oncology research.
To meet these needs, we have developed OncoTree, an open-source cancer classification system. It is maintained by a cross-institutional committee of oncologists, pathologists, scientists, and engineers, accessible via an open-source Web user interface and an application programming interface.
OncoTree currently includes 868 tumor types across 32 organ sites. OncoTree has been adopted as the tumor classification system for American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE), a large genomic and clinical data-sharing consortium, and for clinical molecular testing efforts at Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute. It is also used by precision oncology tools such as OncoKB and cBioPortal for Cancer Genomics.
OncoTree is a dynamic and flexible community-driven cancer classification platform encompassing rare and common cancers that provides clinically relevant and appropriately granular cancer classification for clinical decision support systems and oncology research.
To determine the maximum tolerated dose or maximal administered dose and pharmacokinetic and safety profiles of s.c. administered vascular endothelial growth factor Trap (aflibercept), a novel ...antiangiogenic agent.
In this open-label, dose-escalation study, patients with advanced solid tumors were treated with subcutaneous doses of aflibercept at seven dose levels. Patients received a single dose of aflibercept and then underwent safety and pharmacokinetic assessments over the next 4 weeks. Patients then received weekly or biweekly treatment over the subsequent 6 weeks. Patients tolerating and benefiting could continue on aflibercept at the same dose and schedule until progression of disease.
Thirty-eight patients received at least one dose of aflibercept. Maximum tolerated dose was not reached. Due to solubility/dosing limits with the subcutaneous formulation, 1,600 microg/kg/week was the maximal administered dose. The most common toxicities were proteinuria (37%), fatigue (32%), injection site reactions (18%), nausea (17%), myalgia and anorexia (16% each), hypertension (13%), and voice hoarseness (11%). Drug-related grade 3 to 4 toxicity was uncommon (7%) and reversible: dehydration, cerebral ischemia, proteinuria, hypertension, leukopenia, and pulmonary embolism. We identified dose-proportional increases in plasma concentrations of aflibercept bound to vascular endothelial growth factor with a t(1/2) of 18 days. No antiaflibercept antibodies were detected. Stable disease was maintained for at least 10 weeks in 18 patients (47%), and 2 patients maintained on study for >1 year.
Subcutaneous aflibercept was well tolerated and had manageable side effects. Its favorable pharmacokinetic profile and potential antitumor activity warrants further evaluation.
•A two-tier system (limited- or extensive-stage) has been used for small cell neuroendocrine carcinomas of the cervix.•Concordance probability estimates found that the 2018 FIGO staging system ...predicted outcome better than the two-tier system.•38% of patients had metastases at initial diagnosis, and an additional 38% at subsequent recurrence.•38 patients (60%) had brain imaging: 1 (3%) had brain metastasis at diagnosis and 8 (21%) at subsequent recurrence.•Providers should have a low threshold for brain imaging in patients with advanced disease or neurologic symptoms.
To describe characteristics and outcomes of patients with small cell neuroendocrine carcinoma of the cervix (SCNCC) and determine the staging system most predictive of outcome—the two-tier (limited-stage LS vs. extensive-stage ES) or International Federation of Gynecology and Obstetrics (FIGO) staging system.
Patients with SCNCC evaluated at our institution from 1/1/1990–6/30/2021 were included. Medical records were reviewed for variables of interest. Appropriate statistical tests were performed to determine associations. Survival curves were created using the Kaplan-Meier method. Concordance probability estimates (CPEs) were calculated to evaluate the prediction probability of the staging systems.
Of 63 patients, 41 had LS and 22 ES SCNCC. Patients with ES disease were significantly older than those with LS disease (median, 54 and 37 years, respectively; p < 0.001). Smoking status, race, and history of HPV were not associated with stage or outcomes. Forty-eight patients had metastatic disease (24 50% at initial diagnosis). The most common first sites of metastasis were lung (n = 20/48, 42%), lymph nodes (n = 19/48, 40%), and liver (n = 13/48, 27%). Nine patients had brain metastasis (8 symptomatic at recurrence; 1 asymptomatic at initial diagnosis). Both staging systems were associated with progression-free and overall survival. Adjusted CPE found the FIGO staging system was more predictive of outcomes than the two-tier staging system.
Providers should have a low threshold to obtain brain imaging for patients with SCNCC, especially in the presence of visceral metastases. FIGO staging should be used to classify SCNCC. Further research is necessary to understand prognostic factors of this rare disease.
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