Adjuvant chemotherapy in uterine carcinosarcoma: Comparison of a doublet and a triplet chemotherapeutic regimen.

BACKGROUND: Uterine carcinosarcoma (UCS) is a rare and aggressive malignancy, and there are no existing standard guidelines for adjuvant therapy. Doublet chemotherapy regimens are most favored in adjuvant setting; however, given the early chances of distant recurrences, does a triple-drug adjuvant chemotherapy improve disease-free survival (DFS), remains to be seen. Our aim of the study is to compare and review different adjuvant regimens used in UCS. METHODS: Retrospective chart analysis included 37 optimally staged UCS patients. Each of them had either received paclitaxel plus carboplatin (PC) or paclitaxel, ifosfamide, and cisplatin (TIP). A toxicity analysis was charted as per common terminology criteria for adverse events (CTCAE) 4 criteria. A survival analysis was done by the Kaplan-Meier method, and log-rank test was used for comparison of two variables. RESULTS: Incidence of UCS was 4.1% and mean age (standard deviation) was 58.73 ± 6.3 (range 42 - 71) years. TIP and PC chemotherapies were given to 22 and 15 patients, respectively. Five-year DFS and overall survival for TIP versus PC were 38.2% versus 35.9% (P = 0.118) and 49% versus 50.3% (P = 0.306), respectively, and for Stage I, II versus Stage III was 78.8% versus 12.7%(P = 0.001) and 92.3% versus 34.2% (P = 0.002), respectively. However, in advanced disease (Stage III), there is a trend toward DFS advantage of triple-drug adjuvant regimen (Hazards ratio (HR) = 0.35, 95% confidence interval (CI) = 0.12-1.07). Grade 3 and 4 toxicities were seen in 54.5% patients of TIP chemotherapy group and in 13.3% patients of the PC chemotherapy (P = 0.012). CONCLUSION: Triple-drug adjuvant chemotherapy (TIP) confers no survival advantage over doublet chemotherapy (PC), and in turn, increases the grade 3/4 toxicity in the adjuvant setting of optimally staged UCS patients.

Impact of 2018 ASCO/CAP guidelines on HER-2 reporting categories of IHC and reflex FISH in breast cancer.

Human epidermal growth factor receptor 2 (HER-2) is an established prognostic and predictive biomarker for breast cancer. To ensure accuracy and uniformity for HER-2 testing, ASCO/CAP published guidelines in 2007 which were updated in 2013 and recently in 2018. In this first study from Indian Oncology center, we evaluated the impact of 2018 ASCO/CAP guidelines. We found a substantial decrease in equivocal IHC cases (P-value < .00001). On reclassification, a total of 5.6% cases from equivocal and positive categories (2013 guidelines) shifted to the negative FISH result category (P-value < .0001), with adoption of 2018 guidelines and eliminated the double equivocal cases.

Overview of Breast Cancer and Implications of Overtreatment of Early-Stage Breast Cancer: An Indian Perspective.

The prevalence and mortality of breast cancer is increasing in Asian countries, including India. With advances in medical technology leading to better detection and characterization of the disease, it has been possible to classify breast cancer into various subtypes using markers, which helps predict the risk of distant recurrence, response to therapy, and prognosis using a combination of molecular and clinical parameters. Breast cancer and its therapy, mainly surgery, systemic therapy (anticancer chemotherapy, hormonal therapy, targeted therapy, and immunotherapy), and radiation therapy, are associated with significant adverse influences on physical and mental health, quality of life, and the economic status of the patient and her family. The fear of recurrence and its devastating effects often leads to overtreatment, with a toxic cost to the patient financially and physically in cases in which this is not required. This article discusses some aspects of a breast cancer diagnosis and its impact on the various facets of the life of the patient and her family. It further elucidates the role of prognostic factors, the currently available biomarkers and prognostic signatures, and the importance of ethnically validating biomarkers and prognostic signatures.

Expert Consensus on Effective Management of Chemotherapy-Induced Nausea and Vomiting: An Indian Perspective.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and feared side effects in cancer patients undergoing chemotherapy. Scientific evidence proves its detrimental impact on a patient's quality of life (QoL), treatment compliance, and overall healthcare cost. Despite the CINV-management landscape witnessing a radical shift with the introduction of novel, receptor-targeting antiemetic agents, this side effect remains a chink in the armor of a treating oncologist. Though global guidelines acknowledge patient-specific risk factors and chemotherapeutic agent emetogenic potential in CINV control, a "one-fit-for-all" approach cannot be followed across all geographies. Hence, in a pioneering attempt, India-based oncologists conveyed easily implementable, region-specific, consensus-based statements on CINV prevention and management. These statements resulted from integrating the analysis of scientific evidence and guidelines on CINV by the experts, with their clinical experience. The statements will strengthen decision-making abilities of Indian oncologists/clinicians and help in achieving consistency in CINV prevention and management in the country. Furthermore, this document shall lay the foundation for developing robust Indian guidelines for CINV prevention and control.

Efficacy and tolerability of nimotuzumab in combination with chemotherapy in recurrent and metastatic squamous cell carcinoma of head and neck at a cancer center in Northern India.

INTRODUCTION: Squamous cell carcinoma of head and neck (SCCHN) account for approximately 30-33% of all cancer and the median survival for recurrent and metastatic(R/M) SCCHN remains less than 1 year despite modern advances in therapy. Chemotherapy, usually single agent remains the backbone of therapy in these patients. EGFR antibodies are being used in (R/M) SCCHN. Nimotuzumab is one such agent that has anti-EGFR action similar to other agents without similar skin toxicity. METHODS: Prospective, interventional, non-randomized study done at Rajiv Gandhi Cancer Institute and Research Centre. A total 124 patients were enrolled and divided into Arm A (Chemotherapy + Nimotuzumab) and Arm B (Chemotherapy) in a ratio of 1:1 i.e., 62 in each arm. They were evaluated and treated as per protocol after a written informed consent. Statistical analysis was done using the SPSS software. Quantitative variables were compared using Unpaired t-test/Mann-Whitney Test. Qualitative variables were compared using Chi-Square test /Fisher's exact test. Kaplan-Meier analysis was used to assess the PFS, with log rank test for comparison between the groups. A p value of < 0.05 was considered statistically significant. RESULTS: The most frequent primary location of tumor was oral cavity (n=38, 69%) and (n=33, 56.9%) in both arms. The overall response rate in Arm A was 38.2% and 19% in Arm B (p= 0.023). The disease control rate in Arm A was 74.5% and 43.1% Arm B (p= 0.0007). The median PFS in Arm A was 5.2 months whereas it was 3.2 months in Arm B (p= 0.009). CONCLUSION: In this study, the combination of Nimotuzumab plus platinum/taxane based chemotherapy was active and well tolerated in Indian patients in R/M SCCHN. Addition of Nimotuzumab to chemotherapy had a response rate of 38.2% and median PFS of 5.2 months are strong arguments for clinically testing this combination.

Nab-paclitaxel: An effective third-line chemotherapy in patients with advanced, unresectable gallbladder cancer.

BACKGROUND & OBJECTIVES: Gallbladder (GBC) is an aggressive form of cancer and most patients present with advanced unresectable disease due to lack of early signs and symptoms. This retrospective study was conducted to present the treatment outcomes with three lines of chemotherapies in a subset of patients with advanced, unresectable GBC with the primary objective to determine the response rates with nab-paclitaxel as the third-line chemotherapy after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 (oxaliplatin, leucovorin and 5-FU) therapy. Another objective was to evaluate the toxicity, progression-free survival (PFS) and overall survival (OS). METHODS: Treatment-naive patients with histologically proven inoperable GBC treated with gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel as the first-, second- and third-line chemotherapy were included in this study. The dose of gemcitabine and cisplatin or carboplatin was 1 g/m[2] on days 1 and 8 and 75 mg/m[2] (or target AUC of 5) on day 1, in a 21-day cycle. FOLFOX-4 was administered every two weeks and nab-paclitaxel was administered as 125 mg/m[2] on days 1, 8 and 15 in a 28-day cycle. RESULTS: There were eight men and 13 women with a median age of 57 yr who received nab-paclitaxel therapy. The overall response rate of the first-, second- and third-line chemotherapy was 61.9, 57.1 and 52.4 per cent, respectively. The median PFS for the gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy was 5.5, 5.4 and 2.9 months, respectively. The median OS with three lines of therapies was 14.0 months. Common Terminology Criteria (CTC) grade 3 or 4 haematological toxicities were observed in 28.6, 38.1 and 23.8 per cent of patients on gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy, respectively. INTERPRETATION & CONCLUSIONS: Our study suggests the clinical benefit of nab-paclitaxel chemotherapy in prolonging OS in a selected subgroup of advanced, unresectable GBC patients after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 therapy.

Shared Decision-Making and Medicolegal Aspects: Delivering High-Quality Cancer Care in India.

It is often difficult for people with cancer to make decisions for their care. The aim of this review is to understand the importance of shared decisionmaking (SDM) in Indian clinical scenario and identify the gaps when compared to practices in the Western world. A systematic search (2000-2019) was executed in Medline and Google Scholar using predefined keywords. Of the approximate 400 articles retrieved, 43 articles (Indian: 5; Western: 38) were selected for literature review. Literature review revealed the paucity of information on SDM in India compared to the Western world data. This may contribute to patientreported physical or psychological harms, life disruptions, or unnecessary financial costs. Western world data demonstrate the involvement and sharing of information by both patient and physician, collective efforts of the two to build consensus for preferred treatment. In India, involvement of patients in the planning for treatment is largely limited to tertiary care centers, academic institutes, or only when the cost of therapy is high. In addition, cultural beliefs and prejudices impact the extent of participation and engagement of a patient in disease management. Communication failures have been found to strongly correlate with the medicolegal malpractice litigations. Research is needed to explore ways to how to incorporate SDM into routine oncology practice. India has a high unmet need towards SDM in diagnosis and treatment of cancer. Physicians need to involve patients or their immediate family members in decision making, to make it a patient-centric approach as well. SDM enforces to avoid uninformed decisionmaking or a lack of trust in the treating physician's knowledge and skills. Physician and patient education, development of tools and guiding policies, widespread implementation, and periodic assessments may advance the practice of SDM.

Patterns of epidermal growth factor receptor testing across 111 tertiary care centers in India: Result of a questionnaire-based survey.

BACKGROUND: We conducted a survey of 111 medical oncologists across India to understand the current pattern of epidermal growth factor receptor (EGFR) mutation testing at their respective centers. METHODS: Medical oncologists from 111 institutes across India were interviewed face to face using a structured questionnaire. They were divided into two groups - Group 1 with in-house EGFR testing and Group 2 who send samples to central/commercial laboratories outside their institutions. Answers of the two groups were analyzed to see the prevailing patterns of EGFR testing and differences between the two groups if any. RESULTS: Ninety-five percent (105/111) of medical oncologists recommended testing for EGFR mutations in patients with adenocarcinoma histology and 40% (44/111) recommended EGFR testing in squamous cell histology. The average time duration to get EGFR test results was 10 days in Group 1 centers versus 18 days in Group 2 centers. Ninety-six percent (106/111) of the medical oncologists from Group 1 centers requested for factoring additional sample for biomarker testing compared to 69% (77/111) of the oncologists from Group 2 centers. Sixty-nine percent (77/111) of medical oncologists in Group 1 centers would prefer to wait for the test results before initiating treatment compared to 46% (51/111) in Group 2. EGFR tyrosine-kinase inhibitors were used in only approximately 60% of patients with diagnosed EGFR mutation in the first line. For patients in whom chemotherapy was initiated while waiting for test results, 50% (56/111) of medical oncologists would prefer to complete 4-6 cycles before switching to targeted therapy. At the time of progression, rebiopsy was possible in approximately 25% of the patients. CONCLUSIONS: Turnaround time for molecular testing should improve so that eligible patients can benefit from targeted therapies in the first line. There is a need to increase the awareness among pulmonologists, oncologists, and interventional radiologists regarding the importance of adequate samples required for molecular tests.

Novel formulations of docetaxel, paclitaxel and doxorubicin in the management of metastatic breast cancer.

The management of breast cancer with advanced disease or metastasis is a common problem in India and other countries. A panel of 13 oncology experts deliberated on the sidelines of the 35th Indian Cooperative Oncology Network Conference held in Mumbai to formulate an expert opinion recommendation on the novel drug delivery system (NDDS) formulations in the treatment of metastatic breast cancer (MBC). The survey comprised of 39 questions related to limitations of conventional formulations and therapeutic positioning of NDDS formulations of docetaxel, paclitaxel and doxorubicin in the management of MBC. The experts used data from published literature and their practical experience to provide expert opinion and recommendations for use by the community oncologists. The experts opined that the newer NDDS formulations should provide a significant efficacy advantage in terms of overall survival and progression-free survival, or demonstrate better tolerability when compared with conventional formulations. The newer NDDS formulations of taxanes should be considered in special circumstances such as diabetes, in patients who have had hypersensitivity reactions and in cases where steroids need to be avoided. The novel formulations of doxorubicin should be used in the elderly and in patients with borderline cardiac function.

Gemcitabine with carboplatin for advanced intrahepatic cholangiocarcinoma: A study from North India Cancer Centre.

BACKGROUND: Gemcitabine plus cisplatin has been established as a standard chemotherapy regimen for advanced biliary tract cancers (BTCs) based on the phase III UK ABC-02 study, which included all types of biliary cancers. There is very limited data regarding the effectiveness of known chemotherapeutic regimens especially in IHCC. METHODS: Records of 63 patients diagnosis of IHCC who received Gemcitabine and Carboplatin (G-C Regimen) chemotherapy as a first line were retrospectively reviewed. The primary aim of this study was to assess the response rate of gemcitabine carboplatin-based chemotherapy as a first line therapy in advanced intrahepatic cholangiocarcinoma (IHCC). The secondary objectives were to assess toxicity, progression free survival and overall survival. RESULTS: There were 38 men and 25 women in our study with a median age of 56.75 years (range 31-78 years). Of the 38+25= 63 patients, 21 patients (33.8%) progressed, 5 patients (8.06%) had complete response, 25 patients (40.3%) had partial response, 12 patients (19.3%) had stable disease. Overall response rate was 48.36% and tumor control rate was 67.6%. Progression free survival was 5.3 months and overall survival of 10.3 months was seen. The most common grade 3-4 toxicities were anemia, neutropenia, and thrombocytopenia. Most common nonhematological toxicity was fatigue. CONCLUSION: Gemcitabine in combination with carboplatin has activity against advanced IHCC. Our results are comparable with other gemcitabine carboplatin studies as well as gemcitabine cisplatin-based studies.

Reduced graphene oxide modified smart conducting paper for cancer biosensor.

We report results of the studies relating to the fabrication of a paper based sensor comprising of poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) and reduced graphene oxide (RGO) composite. The effect of various solvents like methanol, ethylene glycol and H2SO4 on the electrical conductivity of PEDOT: PSS coated Whatman paper has been investigated. The conductivity of this solution processed conducting paper significantly increases from ~1.16×10(-4) S cm(-1) up to ~3.57×10(-2) S cm(-1) (~300 times) on treatment with ethylene glycol. The observed significant increase in electrical conductivity is due to conformational rearrangement in the polymer and is due to strong non-covalent cooperative interaction between PEDOT and the cellulose molecules. Further, incorporation of RGO into the conducting paper results in improved electrochemical performance and signal stability. This paper electrode is a promising alternative over the expensive conventional electrodes (ITO, gold and glassy carbon), that are known to have limited application in smart point-of-care (POC) devices. This low cost, flexible and environment friendly conducting paper based biosensor utilized for cancer biomarker (carcinoembryonic antigen, CEA) detection reveals high sensitivity of 25.8 µA ng(-1) mL cm(-2) in the physiological range, 1-10 ng mL(-1).

Antitumor activity and safety of tivozanib (AV-951) in a phase II randomized discontinuation trial in patients with renal cell carcinoma.

PURPOSE: The antitumor activity and safety of tivozanib, which is a potent and selective vascular endothelial growth factor receptor-1, -2, and -3 inhibitor, was assessed in patients with advanced/metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: In this phase II, randomized discontinuation trial, 272 patients received open-label tivozanib 1.5 mg/d (one cycle equaled three treatment weeks followed by a 1-week break) orally for 16 weeks. Thereafter, 78 patients who demonstrated ≥ 25% tumor shrinkage continued to take tivozanib, and 118 patients with less than 25% tumor change were randomly assigned to receive tivozanib or a placebo in a double-blind manner; patients with ≥ 25% tumor growth were discontinued. Primary end points included safety, the objective response rate (ORR) at 16 weeks, and the percentage of randomly assigned patients who remained progression free after 12 weeks of double-blind treatment; secondary end points included progression-free survival (PFS). RESULTS: Of 272 patients enrolled onto the study, 83% of patients had clear-cell histology, 73% of patients had undergone nephrectomy, and 54% of patients were treatment naive. The ORR after 16 weeks of tivozanib treatment was 18% (95% CI, 14% to 23%). Of the 118 randomized patients, significantly more patients who were randomly assigned to receive double-blind tivozanib remained progression free after 12 weeks versus patients who received the placebo (49% v 21%; P = .001). Throughout the study, the ORR was 24% (95% CI, 19% to 30%), and the median PFS was 11.7 months (95% CI, 8.3 to 14.3 months) in the overall study population. The most common grade 3 and 4 treatment-related adverse event was hypertension (12%). CONCLUSION: Tivozanib was active and well tolerated in patients with advanced RCC. These data support additional development of tivozanib in advanced RCC.

A randomized, double-blind, placebo-controlled, phase II study of oral talactoferrin in combination with carboplatin and paclitaxel in previously untreated locally advanced or metastatic non-small cell lung cancer.

INTRODUCTION: The aim of the study is to investigate the activity and safety of oral talactoferrin (TLF) plus carboplatin and paclitaxel (C/P) in patients with previously untreated stage IIIB/IV non-small cell lung cancer. METHODS: Patients (n = 110) were randomly assigned to receive C/P plus either TLF (C/P/T) or placebo (C/P/P). The primary objective of this exploratory study was assessment of confirmed response rate (RR) in the prospectively defined evaluable population with a one-tailed p = 0.05. Secondary objectives included assessment of progression-free survival (PFS), duration of response, overall survival (OS), and safety. RESULTS: The trial met the primary end point of improvement in confirmed RR in the prospectively defined evaluable population. Compared with the C/P/P group, RR increased in the C/P/T group by 18% (29-47%; p = 0.05) and 15% (27-42%; p = 0.08) in the evaluable and intent-to-treat populations, respectively. Compared with the C/P/P group, the C/P/T group had a longer median PFS (4.2 versus 7.0 months), OS (8.5 versus 10.4 months), and duration of response (5.5 versus 7.6 months), although the differences were not statistically significant. Adverse events (AEs) were consistent with C/P therapy. There were fewer total AEs (472 versus 569; two-tailed p = 0.003) and grade 3/4 AEs (78 versus 105; p = 0.05) in the C/P/T group compared with the C/P/P group. CONCLUSION: TLF, in combination with C/P, demonstrated an apparent improvement in RR, PFS, and OS in patients with previously untreated stage IIIB/IV non-small cell lung cancer and appears to enhance activity without significant additional toxicity. These results need to be confirmed in a phase III trial.

Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer.

PURPOSE: This study (EGF20009) assessed the efficacy and tolerability of two lapatinib administration schedules as first-line monotherapy in women with ErbB2-amplified locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Patients with ErbB2-amplified, locally advanced or metastatic breast cancer previously untreated in the metastatic setting were randomly assigned to one of two lapatinib dose cohorts and received either 1,500 mg once daily or 500 mg twice daily. Clinical response was assessed at weeks 8 and 12 and every 12 weeks thereafter. RESULTS: A total of 138 patients were treated with lapatinib for a median of 17.6 weeks. The overall response rate (complete response [CR] plus partial response [PR]) was 24% in the intent-to-treat population, and 31% of patients derived clinical benefit (CR, PR, or stable disease for >or= 24 weeks). The median time to response was 7.9 weeks, and the progression-free survival rates at 4 and 6 months were 63% and 43%, respectively. The most common lapatinib-related adverse events (AEs) were diarrhea, rash, pruritus, and nausea, and these events were primarily grade 1 or 2. There were no significant differences in clinical activity or the AE profile between the dosing schedules. CONCLUSION: Lapatinib demonstrated clinical activity and was well tolerated as first-line therapy in ErbB2-amplified locally advanced or metastatic breast cancer. This study supports further evaluation of lapatinib in first-line and early-stage ErbB2-overexpressing breast cancer.

Breast carcinoma with metastasis to the gallbladder: an unusual case report with a short review of literature.

Gallbladder metastases are very rare and usually arise from malignant melanoma, renal cell carcinoma and cervical carcinoma. Breast carcinoma metastatic to the gallbladder is extremely rare and only 4 cases have been reported in the English literature. We hereby report a 54-year-old lady who was diagnosed as having breast carcinoma and underwent modified radical mastectomy. One month after the operation, she developed acute abdominal pain and underwent cholecystectomy after clinical investigation. Histopathological examination revealed metastasis to the gallbladder. Being considered a patient with metastatic breast carcinoma she was subjected to taxane and anthracycline-based palliative chemotherapy. Later she had CNS involvement and died of the progressive disease soon after few months.

Chronic myeloid leukemia in a man with papillary carcinoma of the thyroid treated with radioactive iodine.

Leukemia as a second malignancy after treatment of thyroid cancer is rare. Most cases reported in the literature have occurred after cumulative doses higher than 800 mCi and it is most commonly acute leukemias. We report a case of chronic myeloid leukemia (CML) occurring in a 40-year-old man 14 years after treatment of papillary thyroid carcinoma. Our patient had the longest interval between the diagnosis of CML and administration of 131I.

Neuroendocrine carcinoma of gallbladder: report of 2 cases.

BACKGROUND: Neuroendocrine carcinoma of the gallbladder is rare. Its best treatment is not known. METHODS: Two patients underwent surgery earlier: one for suspected cholecystitis and the other for cholelithiasis. Magnetic resonance cholangiopancreatography (MRCP) showed residual lesions in the livers. The two patients underwent revision surgery followed by chemotherapy. RESULTS: Both patients tolerated the second stage surgery well, which was followed by chemotherapy with paclitaxel, ifosphamide and cisplatin for 6 cycles. They were treated this way for 8 months and 12 months post treatment, respectively. CONCLUSIONS: A proper diagnosis of neuroendocrine carcinoma is made often after surgery. As it is a slow growing tumor and not very chemotherapeutically, sensitive surgery offers the best local control.

Idoxifene versus tamoxifen: a randomized comparison in postmenopausal patients with metastatic breast cancer.

BACKGROUND: More efficacious and safer hormonal agents are needed for breast cancer treatment and prevention. Idoxifene is a novel selective estrogen receptor modulator (SERM) that, in preclinical models, has greater antiestrogenic but lower estrogenic activity than tamoxifen. PATIENTS AND METHODS: Three hundred and twenty-one postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer were randomized to receive either tamoxifen or idoxifene as initial endocrine therapy for advanced disease. Data were analyzed based on intention to treat and all the responses were subject to independent review. RESULTS: At the time of a second planned interim analysis, the trial was stopped for economic considerations, not for reasons related to safety or efficacy. Complete data for the 219 patients included in the second interim analysis are fully available and reported here. Median age was 59.1 years for idoxifene patients and 59.9 years for tamoxifen patients. Complete response (CR) plus partial response (PR) rates were as follows: tamoxifen, 9%; idoxifene, 13% (P = 0.39). Clinical benefit rate [CR + PR + stable disease (SD) >or=6 months] was 34.3% for idoxifene and 38.7% for tamoxifen (P = 0.31). Median time to progression and duration of response were 140 days and 151.5 days, respectively, for tamoxifen compared with 166 days and 218 days for idoxifene. None of these endpoints was significantly different for the two drugs, nor was survival. Adverse events (lethal, serious but not lethal and important but not life threatening) were similar in the two arms. CONCLUSIONS: Idoxifene was both active and well tolerated in postmenopausal women with metastatic breast cancer. Idoxifene had similar efficacy and toxicity to tamoxifen in this randomized comparison.