Susana Campos - Academia.edu (original) (raw)

Papers by Susana Campos

Clinical Breast Cancer, 2009

Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatmen... more Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatment options for patients who have progressed after tamoxifen therapy include cytotoxic chemotherapy or a trial of a new hormonal therapy. 2 However, with the development of visceral metastases, chemotherapy is the more traditional option because visceral disease is generally considered to be rapidly progressive and possibly resistant to endocrine therapy.

Clinical Breast Cancer, 2009

Breast cancer is the most common malignancy among women, with about one million cases diagnosed e... more Breast cancer is the most common malignancy among women, with about one million cases diagnosed each year worldwide. In the United States, breast cancer is the second leading cause of cancerrelated death in women after lung cancer and the leading cause of cancer-related death in women aged 45−55 years. The human epidermal growth factor receptor 2 (HER2) gene is amplified in 20%−25% of human breast cancers, and overexpression of HER2 is associated with shortened disease-free and overall survival. For 3 decades, doxorubicin has been the most active chemotherapeutic agent in the treatment of advanced breast cancer. Its clinical use is limited by cardiomyopathy and the risk of congestive heart failure (CHF) increasing sharply with lifetime cumulative doxorubicin doses above 450 mg/m 2 . Nonpegylated liposomal doxorubicin (NLD) was designed to reduce the cardiac toxicity of doxorubicin while preserving its antitumor efficacy. This nonpegylated, liposome-encapsulated formulation has a pharmacokinetic profile that is distinct from conventional doxorubicin, resulting in a higher area under the curve, smaller volume of distribution and pattern of biodistribution (substantially reduced uptake into the heart and gastroin-

Journal of Oncology, 2010

Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress... more Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress has been achieved in the treatment of ovarian cancer with therapeutics focused on DNA replication or cell division. However, despite sensitivity to induction chemotherapy the majority of patients will develop recurrent disease. Conventional agents for recurrent disease offer little in terms of long-term responses. Various targeted therapeutics have been explored in the management of ovarian cancer. These include monoclonal antibodies to epidermal growth factor receptors, small molecule tyrosine kinase inhibitors, monoclonal antibodies directed at the vascular endothelial growth factor (bevacizumab), and the small tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor. Recently, several other agents have come forth as potential therapeutic agents in the management of ovarian cancer. These include monoclonal antibodies to the folate receptor, triple angiokinase inhibitors, PARP inhibitors, aurora kinase inhibitors, inhibitors of the Hedgehog pathway, folate receptor antagonists, and MTOR inhibitors.

Journal of Oncology, 2010

Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress... more Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress has been achieved in the treatment of ovarian cancer with therapeutics focused on DNA replication or cell division. However, despite sensitivity to induction chemotherapy the majority of patients will develop recurrent disease. Conventional agents for recurrent disease offer little in terms of long-term responses. Various targeted therapeutics have been explored in the management of ovarian cancer. These include monoclonal antibodies to epidermal growth factor receptors, small molecule tyrosine kinase inhibitors, monoclonal antibodies directed at the vascular endothelial growth factor (bevacizumab), and the small tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor. Recently, several other agents have come forth as potential therapeutic agents in the management of ovarian cancer. These include monoclonal antibodies to the folate receptor, triple angiokinase inhibitors, PARP inhibitors, aurora kinase inhibitors, inhibitors of the Hedgehog pathway, folate receptor antagonists, and MTOR inhibitors.

Clinical Breast Cancer, 2009

Breast cancer is the most common malignancy among women, with about one million cases diagnosed e... more Breast cancer is the most common malignancy among women, with about one million cases diagnosed each year worldwide. In the United States, breast cancer is the second leading cause of cancerrelated death in women after lung cancer and the leading cause of cancer-related death in women aged 45−55 years. The human epidermal growth factor receptor 2 (HER2) gene is amplified in 20%−25% of human breast cancers, and overexpression of HER2 is associated with shortened disease-free and overall survival. For 3 decades, doxorubicin has been the most active chemotherapeutic agent in the treatment of advanced breast cancer. Its clinical use is limited by cardiomyopathy and the risk of congestive heart failure (CHF) increasing sharply with lifetime cumulative doxorubicin doses above 450 mg/m 2 . Nonpegylated liposomal doxorubicin (NLD) was designed to reduce the cardiac toxicity of doxorubicin while preserving its antitumor efficacy. This nonpegylated, liposome-encapsulated formulation has a pharmacokinetic profile that is distinct from conventional doxorubicin, resulting in a higher area under the curve, smaller volume of distribution and pattern of biodistribution (substantially reduced uptake into the heart and gastroin-

Clinical Breast Cancer, 2009

Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatmen... more Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatment options for patients who have progressed after tamoxifen therapy include cytotoxic chemotherapy or a trial of a new hormonal therapy. 2 However, with the development of visceral metastases, chemotherapy is the more traditional option because visceral disease is generally considered to be rapidly progressive and possibly resistant to endocrine therapy.

Cancer, 2001

BACKGROUND. Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity... more BACKGROUND. Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity against ovarian carcinoma. A Phase I-II study in which both drugs were administered concurrently by 96-hour, continuous, intravenous infusion was performed to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy of the combination.

Oncology, 2003

The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxif... more The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxifen has had a substantial impact on mortality in women with early-stage, estrogen-receptor-positive tumors. Despite the improvement in the treatment of breast cancer, many patients will ultimately experience a recurrence. Present treatment approaches can provide effective palliation in the advanced disease setting, but, at best, there has been a modest impact on survival. Numerous options are now available to provide effective palliation for patients with advanced disease. These options include antiestrogens, pure antiestrogens, aromatase inhibitors and progestins and LHRH agonists. Recently, several studies have reviewed the efficacy of aromatase inhibitors as first-line agents in postmenopausal women. Anastrozole and letrozole have recently been approved as first-line agents in women with metastatic breast cancer. In addition to their role in metastatic breast, trials investigating the potential of aromatase inhibitors in the early breast cancer, both in the adjuvant and neoadjuvant setting are underway.

Third-generation aromatase inhibitors are potent inhibitors of the aromatase enzyme, which cataly... more Third-generation aromatase inhibitors are potent inhibitors of the aromatase enzyme, which catalyzes the last step in estrogen biosynthesis. These agents are active against breast cancer in hormone-naïve postmenopausal women and in women who have experienced failure of tamoxifen or failure of tamoxifen plus other hormonal therapy. There are two types of aromatase inhibitors, irreversible steroidal activators (e.g., exemestane) and reversible nonsteroidal imidazole-based inhibitors (e.g., anastrozole, letrozole). Recent data suggest that some women who experience failure of one type of aromatase inhibitor can subsequently derive benefit from the other type. The reason for this lack of cross-resistance is unknown. This finding of non-cross-resistance between steroidal aromatase activators and nonsteroidal aromatase inhibitors offers the opportunity to increase the number of lines of hormone therapy before making the inevitable switch to more toxic chemotherapy, thus potentially improving quality of life for postmenopausal women with advanced disease.

Conventional anthracyclines, particularly doxorubicin, have played an important role in the treat... more Conventional anthracyclines, particularly doxorubicin, have played an important role in the treatment of patients with breast cancer for many decades. Conventional doxorubicin has shown excellent antitumor activity in the metastatic, neoadjuvant, and adjuvant settings. However, its clinical utility is limited due to acute and chronic toxicities, particularly cardiotoxicity, myelosuppression, nausea and vomiting, and alopecia. Liposomal doxorubicin formulations (liposomal doxorubicin [D-99] and pegylated liposomal doxorubicin) currently under investigation for the treatment of breast cancer have demonstrated similar efficacies and favorable toxicity profiles compared with conventional doxorubicin in patients with metastatic breast cancer. These agents have also shown efficacy and tolerability in several small studies as neoadjuvant therapy in patients with locally advanced breast cancer. While there are currently no studies with liposomal doxorubicin or pegylated liposomal doxorubicin as adjuvant therapy, their demonstrated activities and tolerabilities in the metastatic and neoadjuvant settings provide the rationale for the future study of these agents in adjuvant therapy for patients with early-stage breast cancer. The Oncologist 2003;8(suppl 2):10-16

Journal of Psychosocial Oncology, 2012

Malignant ovarian neoplasms represent the leading cause of death in gynecological malignancies. A... more Malignant ovarian neoplasms represent the leading cause of death in gynecological malignancies. Although the majority of ovarian neoplasms occur in women of advanced years, ovarian neoplasms can occur in women of the reproductive age group. Preservation of fertility balanced with treatment of disease is the goal of young patients diagnosed with ovarian neoplasms. A new discipline termed “oncofertility” has emerged; however, several informational gaps exist. Concern has centered on the safety of conservative treatment, the uncertain efficacy of fertility options, the detrimental effects of chemotherapy to remaining reproductive organs, and the timing and execution of fertility workup relative to disease requiring treatment. This study involved an evaluation of young premenopausal women who underwent fertility-sparing surgery for an ovarian neoplasm. Given the rarity of this disease in premenopausal women the objective was to assess the feasibility of this study as defined by the completion rate of the survey. The aim was to broaden our knowledge of patient needs to partner with our survivorship clinic thereby ensuring that patients may facilitate their options. Patients were asked to complete a questionnaire titled Ovarian Cancer or Borderline Malignancy of the Ovary: Fertility Sparing Survey and a previously published instrument termed The Sexual Activity Questionnaire, a 21-item scale that assessed the impact of treatment on sexual functioning. All participants completed the survey illustrating the feasibility of the study. The study revealed that the majority of patients (91%) discussed fertility options with their clinicians, yet only 16% engaged in measures to preserve fertility. Patient's sexual interest and activity was maintained in this cohort of patients. This underscores the importance of continued studies in this unique population to ensure optimal fertility counseling and to better delineate the sexual well-being of young women diagnosed with ovarian neoplasms.

Atlas of Diagnostic Oncology, 2010

Background: Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often re... more Background: Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent. Objective: We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol. Methods: Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records. Results: Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective. Conclusions: Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs. (J Allergy Clin Immunol 2008;122:574-80.)

Gynecologic Oncology, 2004

Background. Topotecan and pegylated liposomal doxorubicin (Doxil) interact with topoisomerase I a... more Background. Topotecan and pegylated liposomal doxorubicin (Doxil) interact with topoisomerase I and II (topo I and II), respectively, with schedule dependent, and potentially synergistic cytotoxicity.Objectives. Define dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) of topotecan delivered by 72-h infusion administered immediately after Doxil delivered at a fixed dose (30 mg/m2) in a cohort of women with recurrent müllerian malignancies.Methods. Topotecan dose was escalated from 0.5 mg/m2/day for 3 days in 0.2 mg/m2/day increments with treatment repeated every 21 days. Eligibility criteria required ECOG ≤2 and no more than four prior lines of chemotherapy. No dose reductions were allowed in the first two cycles to allow evaluation of cutaneous toxicity.Results. Between November 2000 and August 2002, 18 patients were enrolled. Median age 59 (40–71) years. Patients received a median 1 (1–6) cycles of chemotherapy, with 39 cycles of treatment delivered at DL 1. All patients were evaluable for toxicity and 12 for response. At dose level 2, dose-limiting toxicity consisted of nausea and vomiting, mucositis, cutaneous toxicity, and neutropenia. There was no clinically significant cardiac toxicity. There were no radiologically confirmed partial responses.Conclusions. Doxil 30 mg/m2 and topotecan 0.5 mg/m2/day by 72-h infusion (total dose 1.5 mg/m2), although a rational combination of cytotoxic therapies, have limited clinical activity.

Seminars in Oncology, 2002

Anemia is a frequent complication of cancer and its treatment. It often impairs the functional st... more Anemia is a frequent complication of cancer and its treatment. It often impairs the functional status of patients and results in decreased functional capacity and quality of life. Its etiologies are multiple, including chronic inflammation, hemorrhage, nutritional deficiencies, hemolysis, bone marrow suppression by chemotherapy, or infiltration by tumor. It can manifest as feelings of weariness, tiredness, muscular weakness, dysphoric mood, somnolence, or impaired cognitive functioning. In gynecologic patients, the incidence of anemia has been reported to be as high as 80% depending on chemotherapy regimen. Given the various consequences of a low hemoglobin level, the importance of increasing or maintaining hemoglobin levels and ameliorating the symptoms is apparent. Clinical studies have demonstrated that the administration of recombinant human erythropoietin (rHuEPO, epoetin alfa) is effective and safe in increasing hemoglobin levels and improving the overall quality of life in patients with gynecologic cancers undergoing chemotherapy. Therefore, epoetin alfa treatment should be considered in this patient population. Semin Oncol 29 (suppl 8):7-12.

Oncology, 2003

The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxif... more The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxifen has had a substantial impact on mortality in women with early-stage, estrogen-receptor-positive tumors. Despite the improvement in the treatment of breast cancer, many patients will ultimately experience a recurrence. Present treatment approaches can provide effective palliation in the advanced disease setting, but, at best, there has been a modest impact on survival. Numerous options are now available to provide effective palliation for patients with advanced disease. These options include antiestrogens, pure antiestrogens, aromatase inhibitors and progestins and LHRH agonists. Recently, several studies have reviewed the efficacy of aromatase inhibitors as first-line agents in postmenopausal women. Anastrozole and letrozole have recently been approved as first-line agents in women with metastatic breast cancer. In addition to their role in metastatic breast, trials investigating the potential of aromatase inhibitors in the early breast cancer, both in the adjuvant and neoadjuvant setting are underway.

Gynecologic Oncology, 2001

Objectives.The aim of this study was to determine the efficacy and toxicity of single agent off-p... more Objectives.The aim of this study was to determine the efficacy and toxicity of single agent off-protocol, liposomal doxorubicin (Doxil Alza), in consecutive patients with recurrent ovarian cancer and to investigate the influence of HER-2/neu expression on response to liposomal doxorubicin.Patients and methods. Retrospective analysis of 72 consecutive patients treated, typically with liposomal doxorubicin 40 mg/m2 q28 days between January 1997 and December 1998.Results. Twenty-nine patients (40%) had platinum- and taxane-resistant tumors. Nineteen patients (27%) responded with clinical or radiological evidence of response with reduction in CA-125 of >50%. One complete response (CR) and 7 partial responses (PRs) occurred in platinum- and taxane-resistant patients (radiological response (RR) 29%) and 8 PRs occurred in patients with visceral metastases (RR 28%). Time to progression was 5.3 (2.1–12.1) months. Only 7 dose delays (3%) and 20 dose reductions (8%) were necessary in 265 cycles of treatment. Hematological toxicity was generally mild with grade (Gr) ≥III neutropenia in 1 (2%), Gr ≥III thrombocytopenia in 1 (1%), and Gr ≥III anemia in 8 patients (11%). One patient (1%) was admitted with fever and neutropenia. Other toxicity was minimal with Gr ≥III mucositis occurring in 3 patients (4%). Gr ≥III cutaneous toxicity was seen in 6 patients (8%). Three patients (4%) had a >10% fall in ejection fraction but there was no unequivocal clinical heart failure.Conclusions. The data suggest that liposomal doxorubicin is an active drug in both taxane- and platinum-sensitive and resistant recurrent ovarian cancer. Liposomal doxorubicin is associated with tolerable toxicity and is particularly well tolerated in patients with multiple prior lines of treatment.

Gynecologic Oncology, 2009

The objective of this study was to compare the long-term adjustment and QOL of early and advanced... more The objective of this study was to compare the long-term adjustment and QOL of early and advanced stage ovarian cancer survivors (OCS).Early and advanced OCS > 3 years from diagnosis with no evidence of recurrent cancer were interviewed. The following surveys were administered: EORTC QLQ-C30 (overall QOL) and QLQ-OV28 (ovarian specific issues), MHI-17 (anxiety, depression and global well-being), CALGB sexual functioning, FACT Fatigue, Beck's Hopelessness Scale, Fear of Recurrence (FOR), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy (CAM use), and MOS Social Support Survey (MOS). The results of the surveys were compared between the early and advanced stage groups.42 advanced and 58 early stage patients were interviewed. The majority of survivors scored above the medical outpatient norm for emotional status (71% of early stage and 64% of advanced stage survivors). Overall QOL, fatigue, hopelessness, spirituality, social support, degree to which unmet needs were met and use of complementary therapy, did not differ between the two groups. No advanced stage OCS had diagnosable PTSD scores, while 6.9% of early stage survivors had scores indicative of PTSD. Decreased sexual interest attributed to cancer and anxiety when getting CA-125 testing were of concern for both groups. OCS used on average 5 CAM to improve their QOL.Regardless of staging, OCS experience similarly overall positive QOL and adjustment, though PTSD, sexual problems and fear of recurrence are still important for some survivors.

Clinical Breast Cancer, 2009

Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatmen... more Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatment options for patients who have progressed after tamoxifen therapy include cytotoxic chemotherapy or a trial of a new hormonal therapy. 2 However, with the development of visceral metastases, chemotherapy is the more traditional option because visceral disease is generally considered to be rapidly progressive and possibly resistant to endocrine therapy.

Clinical Breast Cancer, 2009

Breast cancer is the most common malignancy among women, with about one million cases diagnosed e... more Breast cancer is the most common malignancy among women, with about one million cases diagnosed each year worldwide. In the United States, breast cancer is the second leading cause of cancerrelated death in women after lung cancer and the leading cause of cancer-related death in women aged 45−55 years. The human epidermal growth factor receptor 2 (HER2) gene is amplified in 20%−25% of human breast cancers, and overexpression of HER2 is associated with shortened disease-free and overall survival. For 3 decades, doxorubicin has been the most active chemotherapeutic agent in the treatment of advanced breast cancer. Its clinical use is limited by cardiomyopathy and the risk of congestive heart failure (CHF) increasing sharply with lifetime cumulative doxorubicin doses above 450 mg/m 2 . Nonpegylated liposomal doxorubicin (NLD) was designed to reduce the cardiac toxicity of doxorubicin while preserving its antitumor efficacy. This nonpegylated, liposome-encapsulated formulation has a pharmacokinetic profile that is distinct from conventional doxorubicin, resulting in a higher area under the curve, smaller volume of distribution and pattern of biodistribution (substantially reduced uptake into the heart and gastroin-

Journal of Oncology, 2010

Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress... more Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress has been achieved in the treatment of ovarian cancer with therapeutics focused on DNA replication or cell division. However, despite sensitivity to induction chemotherapy the majority of patients will develop recurrent disease. Conventional agents for recurrent disease offer little in terms of long-term responses. Various targeted therapeutics have been explored in the management of ovarian cancer. These include monoclonal antibodies to epidermal growth factor receptors, small molecule tyrosine kinase inhibitors, monoclonal antibodies directed at the vascular endothelial growth factor (bevacizumab), and the small tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor. Recently, several other agents have come forth as potential therapeutic agents in the management of ovarian cancer. These include monoclonal antibodies to the folate receptor, triple angiokinase inhibitors, PARP inhibitors, aurora kinase inhibitors, inhibitors of the Hedgehog pathway, folate receptor antagonists, and MTOR inhibitors.

Journal of Oncology, 2010

Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress... more Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress has been achieved in the treatment of ovarian cancer with therapeutics focused on DNA replication or cell division. However, despite sensitivity to induction chemotherapy the majority of patients will develop recurrent disease. Conventional agents for recurrent disease offer little in terms of long-term responses. Various targeted therapeutics have been explored in the management of ovarian cancer. These include monoclonal antibodies to epidermal growth factor receptors, small molecule tyrosine kinase inhibitors, monoclonal antibodies directed at the vascular endothelial growth factor (bevacizumab), and the small tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor. Recently, several other agents have come forth as potential therapeutic agents in the management of ovarian cancer. These include monoclonal antibodies to the folate receptor, triple angiokinase inhibitors, PARP inhibitors, aurora kinase inhibitors, inhibitors of the Hedgehog pathway, folate receptor antagonists, and MTOR inhibitors.

Clinical Breast Cancer, 2009

Breast cancer is the most common malignancy among women, with about one million cases diagnosed e... more Breast cancer is the most common malignancy among women, with about one million cases diagnosed each year worldwide. In the United States, breast cancer is the second leading cause of cancerrelated death in women after lung cancer and the leading cause of cancer-related death in women aged 45−55 years. The human epidermal growth factor receptor 2 (HER2) gene is amplified in 20%−25% of human breast cancers, and overexpression of HER2 is associated with shortened disease-free and overall survival. For 3 decades, doxorubicin has been the most active chemotherapeutic agent in the treatment of advanced breast cancer. Its clinical use is limited by cardiomyopathy and the risk of congestive heart failure (CHF) increasing sharply with lifetime cumulative doxorubicin doses above 450 mg/m 2 . Nonpegylated liposomal doxorubicin (NLD) was designed to reduce the cardiac toxicity of doxorubicin while preserving its antitumor efficacy. This nonpegylated, liposome-encapsulated formulation has a pharmacokinetic profile that is distinct from conventional doxorubicin, resulting in a higher area under the curve, smaller volume of distribution and pattern of biodistribution (substantially reduced uptake into the heart and gastroin-

Clinical Breast Cancer, 2009

Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatmen... more Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatment options for patients who have progressed after tamoxifen therapy include cytotoxic chemotherapy or a trial of a new hormonal therapy. 2 However, with the development of visceral metastases, chemotherapy is the more traditional option because visceral disease is generally considered to be rapidly progressive and possibly resistant to endocrine therapy.

Cancer, 2001

BACKGROUND. Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity... more BACKGROUND. Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity against ovarian carcinoma. A Phase I-II study in which both drugs were administered concurrently by 96-hour, continuous, intravenous infusion was performed to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy of the combination.

Oncology, 2003

The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxif... more The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxifen has had a substantial impact on mortality in women with early-stage, estrogen-receptor-positive tumors. Despite the improvement in the treatment of breast cancer, many patients will ultimately experience a recurrence. Present treatment approaches can provide effective palliation in the advanced disease setting, but, at best, there has been a modest impact on survival. Numerous options are now available to provide effective palliation for patients with advanced disease. These options include antiestrogens, pure antiestrogens, aromatase inhibitors and progestins and LHRH agonists. Recently, several studies have reviewed the efficacy of aromatase inhibitors as first-line agents in postmenopausal women. Anastrozole and letrozole have recently been approved as first-line agents in women with metastatic breast cancer. In addition to their role in metastatic breast, trials investigating the potential of aromatase inhibitors in the early breast cancer, both in the adjuvant and neoadjuvant setting are underway.

Third-generation aromatase inhibitors are potent inhibitors of the aromatase enzyme, which cataly... more Third-generation aromatase inhibitors are potent inhibitors of the aromatase enzyme, which catalyzes the last step in estrogen biosynthesis. These agents are active against breast cancer in hormone-naïve postmenopausal women and in women who have experienced failure of tamoxifen or failure of tamoxifen plus other hormonal therapy. There are two types of aromatase inhibitors, irreversible steroidal activators (e.g., exemestane) and reversible nonsteroidal imidazole-based inhibitors (e.g., anastrozole, letrozole). Recent data suggest that some women who experience failure of one type of aromatase inhibitor can subsequently derive benefit from the other type. The reason for this lack of cross-resistance is unknown. This finding of non-cross-resistance between steroidal aromatase activators and nonsteroidal aromatase inhibitors offers the opportunity to increase the number of lines of hormone therapy before making the inevitable switch to more toxic chemotherapy, thus potentially improving quality of life for postmenopausal women with advanced disease.

Conventional anthracyclines, particularly doxorubicin, have played an important role in the treat... more Conventional anthracyclines, particularly doxorubicin, have played an important role in the treatment of patients with breast cancer for many decades. Conventional doxorubicin has shown excellent antitumor activity in the metastatic, neoadjuvant, and adjuvant settings. However, its clinical utility is limited due to acute and chronic toxicities, particularly cardiotoxicity, myelosuppression, nausea and vomiting, and alopecia. Liposomal doxorubicin formulations (liposomal doxorubicin [D-99] and pegylated liposomal doxorubicin) currently under investigation for the treatment of breast cancer have demonstrated similar efficacies and favorable toxicity profiles compared with conventional doxorubicin in patients with metastatic breast cancer. These agents have also shown efficacy and tolerability in several small studies as neoadjuvant therapy in patients with locally advanced breast cancer. While there are currently no studies with liposomal doxorubicin or pegylated liposomal doxorubicin as adjuvant therapy, their demonstrated activities and tolerabilities in the metastatic and neoadjuvant settings provide the rationale for the future study of these agents in adjuvant therapy for patients with early-stage breast cancer. The Oncologist 2003;8(suppl 2):10-16

Journal of Psychosocial Oncology, 2012

Malignant ovarian neoplasms represent the leading cause of death in gynecological malignancies. A... more Malignant ovarian neoplasms represent the leading cause of death in gynecological malignancies. Although the majority of ovarian neoplasms occur in women of advanced years, ovarian neoplasms can occur in women of the reproductive age group. Preservation of fertility balanced with treatment of disease is the goal of young patients diagnosed with ovarian neoplasms. A new discipline termed “oncofertility” has emerged; however, several informational gaps exist. Concern has centered on the safety of conservative treatment, the uncertain efficacy of fertility options, the detrimental effects of chemotherapy to remaining reproductive organs, and the timing and execution of fertility workup relative to disease requiring treatment. This study involved an evaluation of young premenopausal women who underwent fertility-sparing surgery for an ovarian neoplasm. Given the rarity of this disease in premenopausal women the objective was to assess the feasibility of this study as defined by the completion rate of the survey. The aim was to broaden our knowledge of patient needs to partner with our survivorship clinic thereby ensuring that patients may facilitate their options. Patients were asked to complete a questionnaire titled Ovarian Cancer or Borderline Malignancy of the Ovary: Fertility Sparing Survey and a previously published instrument termed The Sexual Activity Questionnaire, a 21-item scale that assessed the impact of treatment on sexual functioning. All participants completed the survey illustrating the feasibility of the study. The study revealed that the majority of patients (91%) discussed fertility options with their clinicians, yet only 16% engaged in measures to preserve fertility. Patient's sexual interest and activity was maintained in this cohort of patients. This underscores the importance of continued studies in this unique population to ensure optimal fertility counseling and to better delineate the sexual well-being of young women diagnosed with ovarian neoplasms.

Atlas of Diagnostic Oncology, 2010

Background: Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often re... more Background: Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent. Objective: We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol. Methods: Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records. Results: Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective. Conclusions: Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs. (J Allergy Clin Immunol 2008;122:574-80.)

Gynecologic Oncology, 2004

Background. Topotecan and pegylated liposomal doxorubicin (Doxil) interact with topoisomerase I a... more Background. Topotecan and pegylated liposomal doxorubicin (Doxil) interact with topoisomerase I and II (topo I and II), respectively, with schedule dependent, and potentially synergistic cytotoxicity.Objectives. Define dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) of topotecan delivered by 72-h infusion administered immediately after Doxil delivered at a fixed dose (30 mg/m2) in a cohort of women with recurrent müllerian malignancies.Methods. Topotecan dose was escalated from 0.5 mg/m2/day for 3 days in 0.2 mg/m2/day increments with treatment repeated every 21 days. Eligibility criteria required ECOG ≤2 and no more than four prior lines of chemotherapy. No dose reductions were allowed in the first two cycles to allow evaluation of cutaneous toxicity.Results. Between November 2000 and August 2002, 18 patients were enrolled. Median age 59 (40–71) years. Patients received a median 1 (1–6) cycles of chemotherapy, with 39 cycles of treatment delivered at DL 1. All patients were evaluable for toxicity and 12 for response. At dose level 2, dose-limiting toxicity consisted of nausea and vomiting, mucositis, cutaneous toxicity, and neutropenia. There was no clinically significant cardiac toxicity. There were no radiologically confirmed partial responses.Conclusions. Doxil 30 mg/m2 and topotecan 0.5 mg/m2/day by 72-h infusion (total dose 1.5 mg/m2), although a rational combination of cytotoxic therapies, have limited clinical activity.

Seminars in Oncology, 2002

Anemia is a frequent complication of cancer and its treatment. It often impairs the functional st... more Anemia is a frequent complication of cancer and its treatment. It often impairs the functional status of patients and results in decreased functional capacity and quality of life. Its etiologies are multiple, including chronic inflammation, hemorrhage, nutritional deficiencies, hemolysis, bone marrow suppression by chemotherapy, or infiltration by tumor. It can manifest as feelings of weariness, tiredness, muscular weakness, dysphoric mood, somnolence, or impaired cognitive functioning. In gynecologic patients, the incidence of anemia has been reported to be as high as 80% depending on chemotherapy regimen. Given the various consequences of a low hemoglobin level, the importance of increasing or maintaining hemoglobin levels and ameliorating the symptoms is apparent. Clinical studies have demonstrated that the administration of recombinant human erythropoietin (rHuEPO, epoetin alfa) is effective and safe in increasing hemoglobin levels and improving the overall quality of life in patients with gynecologic cancers undergoing chemotherapy. Therefore, epoetin alfa treatment should be considered in this patient population. Semin Oncol 29 (suppl 8):7-12.

Oncology, 2003

The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxif... more The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxifen has had a substantial impact on mortality in women with early-stage, estrogen-receptor-positive tumors. Despite the improvement in the treatment of breast cancer, many patients will ultimately experience a recurrence. Present treatment approaches can provide effective palliation in the advanced disease setting, but, at best, there has been a modest impact on survival. Numerous options are now available to provide effective palliation for patients with advanced disease. These options include antiestrogens, pure antiestrogens, aromatase inhibitors and progestins and LHRH agonists. Recently, several studies have reviewed the efficacy of aromatase inhibitors as first-line agents in postmenopausal women. Anastrozole and letrozole have recently been approved as first-line agents in women with metastatic breast cancer. In addition to their role in metastatic breast, trials investigating the potential of aromatase inhibitors in the early breast cancer, both in the adjuvant and neoadjuvant setting are underway.

Gynecologic Oncology, 2001

Objectives.The aim of this study was to determine the efficacy and toxicity of single agent off-p... more Objectives.The aim of this study was to determine the efficacy and toxicity of single agent off-protocol, liposomal doxorubicin (Doxil Alza), in consecutive patients with recurrent ovarian cancer and to investigate the influence of HER-2/neu expression on response to liposomal doxorubicin.Patients and methods. Retrospective analysis of 72 consecutive patients treated, typically with liposomal doxorubicin 40 mg/m2 q28 days between January 1997 and December 1998.Results. Twenty-nine patients (40%) had platinum- and taxane-resistant tumors. Nineteen patients (27%) responded with clinical or radiological evidence of response with reduction in CA-125 of >50%. One complete response (CR) and 7 partial responses (PRs) occurred in platinum- and taxane-resistant patients (radiological response (RR) 29%) and 8 PRs occurred in patients with visceral metastases (RR 28%). Time to progression was 5.3 (2.1–12.1) months. Only 7 dose delays (3%) and 20 dose reductions (8%) were necessary in 265 cycles of treatment. Hematological toxicity was generally mild with grade (Gr) ≥III neutropenia in 1 (2%), Gr ≥III thrombocytopenia in 1 (1%), and Gr ≥III anemia in 8 patients (11%). One patient (1%) was admitted with fever and neutropenia. Other toxicity was minimal with Gr ≥III mucositis occurring in 3 patients (4%). Gr ≥III cutaneous toxicity was seen in 6 patients (8%). Three patients (4%) had a >10% fall in ejection fraction but there was no unequivocal clinical heart failure.Conclusions. The data suggest that liposomal doxorubicin is an active drug in both taxane- and platinum-sensitive and resistant recurrent ovarian cancer. Liposomal doxorubicin is associated with tolerable toxicity and is particularly well tolerated in patients with multiple prior lines of treatment.

Gynecologic Oncology, 2009

The objective of this study was to compare the long-term adjustment and QOL of early and advanced... more The objective of this study was to compare the long-term adjustment and QOL of early and advanced stage ovarian cancer survivors (OCS).Early and advanced OCS > 3 years from diagnosis with no evidence of recurrent cancer were interviewed. The following surveys were administered: EORTC QLQ-C30 (overall QOL) and QLQ-OV28 (ovarian specific issues), MHI-17 (anxiety, depression and global well-being), CALGB sexual functioning, FACT Fatigue, Beck's Hopelessness Scale, Fear of Recurrence (FOR), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy (CAM use), and MOS Social Support Survey (MOS). The results of the surveys were compared between the early and advanced stage groups.42 advanced and 58 early stage patients were interviewed. The majority of survivors scored above the medical outpatient norm for emotional status (71% of early stage and 64% of advanced stage survivors). Overall QOL, fatigue, hopelessness, spirituality, social support, degree to which unmet needs were met and use of complementary therapy, did not differ between the two groups. No advanced stage OCS had diagnosable PTSD scores, while 6.9% of early stage survivors had scores indicative of PTSD. Decreased sexual interest attributed to cancer and anxiety when getting CA-125 testing were of concern for both groups. OCS used on average 5 CAM to improve their QOL.Regardless of staging, OCS experience similarly overall positive QOL and adjustment, though PTSD, sexual problems and fear of recurrence are still important for some survivors.