Reconstructive Options for Basal Cell Carcinoma Defects in the Head and Neck Region: An Institutional Experience.

Basal cell carcinoma (BCC) is the most common skin cancer with more than 80% occurring on the face occurring mainly due to exposure to ultraviolet rays in the elderly due to cumulative exposure of the UV rays during their lifetime. Though various treatment modalities are available for the treatment of basal cell carcinomas, wide local excision is the standard line of management. However, reconstruction of facial BCC poses a challenge to the reconstructive surgeon. Over a 4-year-old period from 2017 to 2021, a total of 30 patients of head and neck basal cell carcinoma were surgically excised in our institution. We have explored all modes of reconstruction from small to large BCC defects in terms of cosmesis, form and function. Four patients underwent primary closure, 8 patients underwent skin grafting, 13 patients underwent closure by local and advancement flaps and 5 patients with large defects underwent free flap reconstruction. No flap loss was reported. None reported any functional deficit. To achieve adequate aesthetic surgical outcomes after reconstruction, knowledge of facial aesthetic regions is of utmost importance. The size and location of the defect and the presence of vital structures adjacent to the defect should be assessed to determine the kind of reconstruction that should be carried out without adversely affecting adjacent structures. For greater patient satisfaction, the method of reconstruction should be tailor made, where donor tissue resembles native tissue with good contour and texture match, suture line scars are camouflaged, and complications are nil.

Lingual Artery as the Recipient Vessel of Choice in Patients Requiring a Second or Third Free Flap in Recurrent Oral Cancers and Vessel-Depleted Neck: A 5-Year Experience in a Single Institute.

Introduction Reconstruction with free flaps becomes a challenge in recurrent cases having previously treated necks, in patients who have received prior radiation therapy or chemotherapy or both, and where the patient has already undergone free flap reconstruction in a prior surgery. Depleted cervical recipient vessels can increase the complexity of reconstruction in achieving successful free flap prefusion and thereby increasing flap thrombosis and eventually failure. Materials and Methods Over a period of 5 years from January 2018 to February 2023, we encountered a total of 22 cases of recurrent or second primary oral cancer with bilateral necks operated, postadjuvant chemo-radiotherapy, and requiring a second or third free flap reconstruction. In most of the cases we resorted to the lingual artery as the recipient artery of choice. Results No flap loss was reported. No cases were reexplored either for hematoma or for congestion. All patients recovered uneventfully. Conclusion To the best of our knowledge, there has been no paper yet that focuses on the lingual artery to be the recipient vessel of choice in recurrent oral cancers. We find the lingual artery to be a reliable and safe option and advocate its usage as recipient vessel of choice in recurrent oral cancers requiring more than one free flap reconstruction.

Translation and Pilot Validation of the EORTC QLQ-NHL-HG29 Module in Indian Languages (Hindi and Marathi) for Use in Indian Patients with Non-Hodgkin's Lymphoma.

Roshankumar PatilBackground Cancer and its related treatments have a huge impact on a patient's quality of life (QOL). To measure such QOL in cancer patients, the European Organization for Research and Treatment of Cancer (EORTC) has introduced various scales/questionnaires for various cancers. In the present study, we aimed to translate and validate high-grade Non-Hodgkin's lymphoma (NHL-HG) English questionnaire (EORTC QLQ-NHL-HG29) into Hindi and Marathi (two of the most popular Indian language) to make it available for patients and the scientific community. Materials and methods The EORTC QLQ-NHL-HG29 was translated into Hindi and Marathi languages as per EORTC guidelines. The translated questionnaire was pilot-tested in a sample of 20 patients (10 for each translation) with NHL-HG. Results After procuring required approvals from EORTC, the existing QLQ-NHL-HG29 English questionnaire was translated (forward and backward) into vernacular languages (Hindi and Marathi). Later, the translations were sent to EORTC for evaluation and all the queries raised by EORTC toward translations were discussed and included in the final questionnaires as per EORTC guidelines. On receiving approval from EORTC translation coordinator, pilot study was conducted in 20 patients. In the pilot study, 10 patients were given the Hindi questionnaire and other 10 patients were given the Marathi questionnaire. Based on the pilot testing interpretations or suggestions from the patients, all the necessary modifications were incorporated in the questionnaires and sent to EORTC for validation and approval. Conclusion Both the translations (Hindi and Marathi) submitted to the EORTC have now been approved (QLQ-NHL-HG29) by the EORTC-QOL unit and after procuring necessary permissions from the EORTC both of these translations can be used reliably in clinical practice and clinical trials to assess QOL in patients suffering from NHL-HG.

Exploring the Aggressiveness of Sarcomatoid Carcinoma of the Oral Cavity - an Institutional Experience.

Background: Sarcomatoid variant of squamous cell carcinoma in the oral cavity is a rare biphasic variant of squamous cell carcinoma. This aggressive variant of squamous cell carcinoma is characterized by invasive growth with marked local recurrence and distant metastasis resulting in poor prognosis. Sarcomatoid carcinoma can occur over a wide age range, incidence increases with older age and is a male-predominant disease. Methods: 23 patients with histologically proven Sarcomatoid SCC or with a sarcomatoid component (Group A) were compared with 23 randomly chosen patients with clinical stage IV (Group B) disease at the time of diagnosis, within the same time period and comparison was made between disease free survival and overall survival. Results: In group A, the mean DFS was found to be 12.4 months raging from 1 month to 36 months. 6 patients were therafter lost to follow follow up, in 11 patients the mean overall survival was found to be 8.72 months (ranging from 2 to 18 months) whereas 6 patients are alive till date. In group B, the mean DFS was found to be 19.56 months ranging from 6 months to 33 months. 4 patients succumbed to the disease with a mean overall survival of 24.25 years (ranging from 18 to 33 months), 4 patients were lost to follow up and the rest are alive till date. Conclusion: Sarcomatoid carcinoma of the oral cavity is an extremely rare but aggressive variant of conventional squamous cell carcinoma. We have to systematically understand their clinical, morphological and immunohistochemical features which is critical for their accurate diagnosis which aids in correct patient management. After radical surgery and adjuvant radiation therapy, strict follow up for development of recurrence and distant metastasis should be done.

Depth of Invasion, Lymphovascular Invasion, and Perineural Invasion as Predictors of Neck Node Metastasis in Early Oral Cavity Cancers.

Aims: The present study examines the role of demographic and pathological features of primary tumours in predicting neck metastasis in early oral cavity cancers, which has been a matter of debate. Methods: A single-centre, retrospective, institution review was conducted of all the patients presented to our centre from January 2014 to December 2021. Patient characteristics were compared between the two lymph node groups (lymph node positive and lymph node negative) and significant prognostic factors were determined. Results: A total of 462 oral squamous cell carcinoma (OSCC) patients were included, 407 male and 55 female. Tobacco chewing (59.2%) was a major habit with buccal mucosa (49.5%) and tongue (44.8%) as primary sites. The majority of the patient's histology was of SCC (96.8%) with grade II (moderately differentiated, 74.5%). Univariate logistic regression analysis to predict lymph node metastasis showed pT size (< 0.001), LVI (< 0.001), and PNI (< 0.001) as significant tumor characteristics. On multivariate, pT size (OR-1.58, P - 0.0001) and LVI (OR-19.70, P - 0.0001) were reported to be statistically significant to predict lymph node metastasis. Conclusion: Reporting and studying the clinico-pathological features of primary tumors can give vital information in predicting the neck node metastasis in OSCC patients.

Comparative evaluation of oral mucositis in oral cancer patients undergoing 3-dimensional conformal radiation therapy and intensity modulated radiation therapy with or without chemotherapy.

Context: Oral cancer is a significant cause of death across the world. A combined multimodal approach integrating surgery and radiation therapy (RT) with or without chemotherapy (CT) is commonly employed in advanced oral cancer to prevent recurrences and locoregional spread. Oral mucositis is a common acute toxicity reported in patients undergoing RT and CT. The delivery of optimal cancer therapy protocols is compromised due to morbidity caused by oral mucositis. Aims: To compare the severity of oral mucositis in oral cancer patients undergoing 3-Dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) with or without concomitant CT. Settings and Design: This was a prospective, unicentric and longitudinal study conducted in a cancer centre. Methods and Material: One hundred four patients with locally advanced oral cancer were enrolled in this study. Fifty-two patients were treated with IMRT and 52 patients with 3DCRT to a dose of >60 Gy, along with concurrent cisplatin weekly CT. Mucositis was recorded before the start, in the end, 1 month, and 3 months post-chemoradiotherapy treatment. Statistical Analysis Used: Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software (v. 21.0, Chicago. 2012). Descriptive and frequency statistics were performed for different parameters assessed in 3DCRT and IMRT group. Results: Grade 3 mucositis was the most predominant grade observed in both groups at the end of treatment. Thirty-six patients (69.3%) versus 24 patients (46.1%) developed grade 3 mucositis in 3DCRT and IMRT group, respectively (P = 0.013). Healing was better with IMRT group when compared to 3DCRT group 1 month and 3 months post-RT. Mucositis was severe in patients undergoing concomitant CT. Conclusions: IMRT reduced the incidence of severe mucositis and also improved the treatment-compliance compared to 3DCRT in locally advanced head neck cancer patients treated by chemoradiotherapy.

Psychological and Mental Health Burden on Health Care Providers in a Cancer Centre during COVID-19 Pandemic Outbreak in India.

BACKGROUND: The outbreak of novel coronavirus (COVID-19) is severely affecting the public health and posing a challenge to health care providers, especially working as front-line medical staff. This study was aimed to understand the psychological impact and mental burden of the present outbreak on Indian health care providers who are working at cancer care centre. SUBJECTS AND METHODS: A self-reporting online questionnaire was given to the multidisciplinary staff (n=344) and their mental health was assessed using various scales via GAD-7 scale for anxiety, PHQ-9 scale for depression, ISI for insomnia, K-10 for distress, and STAI for stress along with five self-made Pandemic specific questions. RESULTS: Response rate was 91% (n=344) among 190 (55%) were male and 154 (45%) were female. The frontline and second-line workers were 178 (52%) and 166 (48%), respectively. Symptoms of anxiety, depression, insomnia and distress was observed in 62 (18%), 75 (22%), 42 (12%), and 60 (17%) of the participants, respectively. They were predominantly influenced by variables such as gender (female), education (≥graduation), co-morbidities, and level of work (frontline). Followed by other less dominant variables such as contact with patients (frequent), and working in hospital (<3 years), respectively. CONCLUSION: A mild to moderate level of psychological burden was observed in the health care providers. Overall, there is a need to address the mental health issues by providing, timely training, counselling, rotation in shifts, lowering workload and inten¬sify the awareness programmes of the staff during this COVID-19 pandemic for better outcomes and promoting resilience in the staff.

The predictive role of neutrophil-to-lymphocyte ratio in the outcomes of patients with sarcomatoid carcinoma of oral cavity.

INTRODUCTION: The aim of the present study was to evaluate the prognostic value of the inflammatory response biomarkers and their impact on survival outcomes in the patients with sarcomatoid carcinoma (SC) of oral cavity, a rare variant of squamous cell carcinoma (SqC). MATERIALS AND METHODS: Seventeen patients diagnosed with SC of oral cavity without metastases treated between Jan 2017 to June 2020 were identified and included in the present study. Pre- and post-operative inflammatory biomarkers and other prognostic markers were evaluated and their impact on disease-free survival (DFS) and overall survival (OS) was studied. RESULTS: Seventeen patients (16 males and one female) were included in the present study with a median age of 42 years (IQR: 26-76 years). With the median follow-up of 15 months, nine of 17 patients had developed recurrence and were succumbed to either locoregional recurrence or distant progression. One-year Kaplan-Meier estimates of DFS and OS were 57% and 58.3% respectively. On univariate analysis, baseline NLR, PLR, and pathological bone/skin involvement were identified to be significant prognostic factors affecting the patient's DFS and OS. On multi-variate analysis, baseline NLR > 3 and pathological bone or skin involvement by tumour were emerged as some independent significant predictors. CONCLUSION: For the first time, the predictive role of inflammatory markers is studied and proven significant affecting patients' survival outcomes. Hence, these inflammatory biomarkers may be considered for routine clinical use as reliable and low-cost prognostic markers to tailor the management of SC of oral cavity.

My Journey of Becoming a Doctorpreneur-Transforming Dream into Reality.

The dream of bringing affordable, accessible, and quality cancer care to the people is my dream, and it took me almost over a decade to turn it into reality. My dream took its shape in 2007 by starting Manavata Cancer Centre, a 75-bed regional cancer centre in Nashik, Maharashtra. We then collaborated with Dr. Ajai Kumar of Health Care Global Enterprises and added 200 additional beds making a total of 275 oncology beds dedicated exclusively to treat cancer patients. Over the years, we have emerged as a complete comprehensive cancer care centre with a team of 700 + members, ensuring multidisciplinary care under one roof. We have always kept ourselves forefront in terms of bringing advanced technology to our patients and in conducting various academic programs (DNB programs, breast and head and neck fellowships and industry-sponsored clinical trials etc.) for academic advancement. As of date, > 95,000 patients were treated at our centre and > 50,000 ladies were screened under our women's health initiative program - Arogya Saheli.

Elective Surgical Experience During COVID Pandemic at a Tertiary Cancer Care Centre in India: A Retrospective Analysis.

To analyse and identify possible outcomes of elective cancer surgeries performed at a tertiary cancer centre during COVID19 pandemic. This is a retrospective study including patients that underwent surgery at HCG Manavata cancer centre, Nashik, Maharashtra, India, from 15 March 2020 to 15 June 2020. Among the 458 patients that underwent elective surgeries, 54% were male and 46% were female, with a median age of 50.57 years. The most common sites of cancer distribution were head and neck (24.67%), colorectal (11.57%), gynaecological (11.35%), and breast (10.26%). Of the included patients, 92% were of American Society of Anaesthesiologists (ASA) II with comorbidities such as hypertension, and 64% underwent major surgeries with a mortality rate of 1.52% (n = 7). Average duration of surgery and hospital stay was observed to be 168.43 min and 4.4 days, respectively. Post-operatively, 7 patients were tested COVID positive and their recovery was uneventful. Despite the difficulty that set in because of COVID19 pandemic, it was proven from our study that elective cancer care surgeries can be successfully performed by following all the set guidelines.

Evaluation of Prognostic Factors that Affect Survival Outcomes of Breast Cancer Patients with Brain Metastases: A Single Institutional Experience.

OBJECTIVE: This study aimed to evaluate various prognostic factors that play a vital role in stratifying and guiding tailored treatment strategies and survival outcome in breast cancer patients with brain metastases (BM). MATERIALS AND METHODS: Data regarding demography, clinical presentation, molecular subtypes, risk-stratification, treatment details, and outcomes were retrieved from medical records. All time-to-event (survival) outcomes were analyzed by Kaplan-Meir method and compared using log-rank test. Univariate and multivariate analysis of relevant prognostic factors were performed and p-values ≤0.05 were considered statistically significant. RESULTS: A total of 88 patients (median age: 50 years) were included for this study. The median follow-up time of all surviving patients was ~20 months. During the follow-up, 82 (93.1%) patients died. The median survival of all patients was 12 months, with 1-year and 2-year overall survival (OS) rate of 51% and 22%, respectively. Based on univariate analysis, statistically significant prognostic factors for OS were molecular subtypes, number of BM, and Karnofsky Performance Status (KPS); however, number of BM and KPS emerged as independent predictors of survival based on multivariate analysis. CONCLUSION: We conclude that, there are other important prognostic factor, such as number of BM, which may affect the OS of these patients, in addition to variables included in the diagnosis-specific graded prognostic assessment score. Prospective studies evaluating these factors are necessary to further refine the stratification of patients, which will aid the initiation of appropriate treatment to improve the OS of patients.

Safety and efficacy of scalp cooling system in preventing chemotherapy induced alopecia - A single center prospective study.

BACKGROUND: Alopecia is one of the most common and afflicting side effects associated with chemotherapy treatments. Scalp-cooling devices were introduced to reduce hair loss and improve the hair volume recovery in patients undergoing chemotherapy. METHODS: This is a single center, prospective observational study conducted from 01 February 2019 to 31 January 2020, in patients undergoing chemotherapy for various cancers. The extent of alopecia was assessed by two independent clinicians by reviewing the photographs taken at baseline, during each session, and 4 weeks from the last scalp cooling session. RESULTS: A total of 100 patients (female: 94 and male: 6) were enrolled in the study, with a mean age of 53.5 years. Of 100 patients, 40 received anthracycline based chemotherapy, 45 received taxane based chemotherapy, 9 received both, and 6 received other chemotherapeutic agents. By the end of the study, 31 patients experienced grade 0-1 alopecia and 69 patients had grade 2 alopecia. On multivariate analysis, chemotherapeutic agent was found to be an independent factor for delaying the onset of Grade 2 alopecia (anthracycline vs taxanes (OR: 0.71; 95% CI (0.51-0.92); P ≤ 0.04)The most common adverse events reported during the scalp cooling sessions were chills (7%), and chills with headaches (6%). Scalp metastasis and scalp cooling discontinuation rates were observed to be very rare. No serious adverse events related to device were observed. CONCLUSION: Scalp cooling was observed to be more effective in reducing chemotherapy-induced alopecia in patients treated with taxane-based chemotherapy over anthracyclines. Scalp cooling sessions were well tolerated. Scalp metastasis and scalp cooling discontinuation was observed to be very rare.

Patterns of blood pressure changes in patients with head and neck cancer receiving radiotherapy or chemo-radiotherapy at a tertiary cancer centre.

BACKGROUND: To evaluate patterns of blood pressure (BP) changes in patients with head and neck cancer (HNC) receiving radiation (RT)/chemo-radiation (CRT) METHODS: This study included data collection, compilation, and analysis of 451 consecutive HNC patients who underwent RT/CRT. RESULTS: Out of 451 patients, 376 (82%) were male and 75 (18%) were female with a median age of 52 years. Patients receiving 3DCRT experienced greater fall in BP, including for SBP and MAP, compared to those receiving IMRT-IGRT. Female patients experienced greater fall in diastolic BP as compared to male patients (p: 0.03). At the end of treatment, we observed a significant association between a fall in systolic BP (decrease by 10% of baseline) and weight loss of more than 10% of baseline weight (p: 0.03). CONCLUSION: Fall in BP during RT/CRT is significantly affected by treatment technique and sex and is strongly associated with significant weight loss.

Sarcomatoid Carcinoma of the Penis: An Uncommon Penile Neoplasm.

Sarcomatoid squamous cell carcinomas are extremely rare, high grade, aggressive variant of penile cancers. Sarcomatoid carcinoma are biphasic neoplasms with a combination of both sarcomatoid components and carcinomatous elements. These neoplasms are very rare in the urogenital system. We report a 53-year-old male presented with an ulcerated lesion on the glans penis. The rarity of this case reiterates the importance of thorough morphological and histological examination along with immunohistochemistry in diagnosing, staging, treatment and follow up of patients.

Diplopia-an unheralded consequence of neck dissection: case report.

INTRODUCTION: Neck dissection is a part of the standard surgical procedure in the management of head and neck malignancy. Diplopia following neck dissection is a rare entity; hence, its diagnosis and management strategies needed to be discussed for prevention of its grave consequences. CASE REPORT: A 30-year-old male patient presented with binocular horizontal diplopia following total thyroidectomy and neck dissection. On evaluation, there was internal jugular vein (IJV) thrombosis followed by cerebral venous sinus thrombosis (CVST). After meticulous medical management with diuretics and antiplatelet drugs, diplopia resolved completely and normal vision was restored. CONCLUSION: Therapeutic ligation of internal jugular vein during neck dissection may result in IJV thrombosis followed by CVST leading to raised intracranial tension (ICT). It has to be anticipated and addressed as early as possible to prevent its grave consequences like blindness and death.

Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with epithelial malignancies. We assessed whether the addition of buparlisib to paclitaxel improves clinical outcomes compared with paclitaxel and placebo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. METHODS: In this multicentre, randomised, double-blind, placebo-controlled phase 2 study (BERIL-1), we recruited patients aged 18 years and older with histologically or cytologically confirmed recurrent and metastatic squamous cell carcinoma of the head and neck after disease progression on or after one previous platinum-based chemotherapy regimen in the metastatic setting. Eligible patients were enrolled from 58 centres across 18 countries and randomly assigned (1:1) to receive second-line oral buparlisib (100 mg once daily) or placebo, plus intravenous paclitaxel (80 mg/m2 on days 1, 8, 15, and 22) in 28 day treatment cycles. Randomisation was done via a central patient screening and randomisation system with an interactive (voice and web) response system and stratification by number of previous lines of therapy in the recurrent and metastatic setting and study site. Patients and investigators (including local radiologists) were masked to treatment assignment from randomisation until the final overall survival analysis. The primary endpoint was progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in all randomly assigned patients. Efficacy analyses were done on the intention-to-treat population, whereas safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov, number NCT01852292, and is ongoing but no longer enrolling patients. FINDINGS: Between Nov 5, 2013, and May 5, 2015, 158 patients were enrolled and randomly assigned to receive either buparlisib plus paclitaxel (n=79) or placebo plus paclitaxel (n=79). Median progression-free survival was 4·6 months (95% CI 3·5-5·3) in the buparlisib group and 3·5 months (2·2-3·7) in the placebo group (hazard ratio 0·65 [95% CI 0·45-0·95], nominal one-sided p=0·011). Grade 3-4 adverse events were reported in 62 (82%) of 76 patients in the buparlisib group and 56 (72%) of 78 patients in the placebo group. The most common grade 3-4 adverse events (occurring in ≥10% of patients in the buparlisib group vs the placebo group) were hyperglycaemia (17 [22%] of 76 vs two [3%] of 78), anaemia (14 [18%] vs nine [12%]), neutropenia (13 [17%] vs four [5%]), and fatigue (six [8%] vs eight [10%]). Serious adverse events (regardless of relation to study treatment) were reported for 43 (57%) of 76 patients in the buparlisib group and 37 (47%) of 78 in the placebo group. On-treatment deaths occurred in 15 (20%) of 76 patients in the buparlisib group and 17 (22%) of 78 patients in the placebo group; most were caused by disease progression and none were judged to be related to study treatment. INTERPRETATION: On the basis of the improved clinical efficacy with a manageable safety profile, the results of this randomised phase 2 study suggest that buparlisib in combination with paclitaxel could be an effective second-line treatment for patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck. Further phase 3 studies are warranted to confirm this phase 2 finding. FUNDING: Novartis Pharmaceuticals Corporation.

Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer.

PURPOSE: To estimate the efficacy and toxicity of AMG 386, an investigational peptide-Fc fusion protein that neutralizes the interaction between the Tie2 receptor and angiopoietin-1/2, plus weekly paclitaxel in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned 1:1:1 to receive paclitaxel (80 mg/m(2) once weekly [QW], 3 weeks on/1 week off) plus intravenous AMG 386 10 mg/kg QW (arm A), AMG 386 3 mg/kg QW (arm B), or placebo QW (arm C). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response, CA-125 response, safety, and pharmacokinetics. RESULTS: One hundred sixty-one patients were randomly assigned. Median PFS was 7.2 months (95% CI, 5.3 to 8.1 months) in arm A, 5.7 months (95% CI, 4.6 to 8.0 months) in arm B, and 4.6 months (95% CI, 1.9 to 6.7 months) in arm C. The hazard ratio for arms A and B combined versus arm C was 0.76 (95% CI, 0.52 to 1.12; P = .165). Further analyses suggested an exploratory dose-response effect for PFS across arms (Tarone's test, P = .037). Objective response rates for arms A, B, and C were 37%, 19%, and 27%, respectively. The incidence of grade ≥ 3 adverse events (AEs) in arms A, B, and C was 65%, 55%, and 64%, respectively. Frequent AEs included hypertension (8%, 6%, and 5% in arms A, B, and C, respectively), peripheral edema (71%, 51%, and 22% in arms A, B, and C, respectively), and hypokalemia (21%, 15%, and 5% in arms A, B, and C, respectively). AMG 386 exhibited linear pharmacokinetic properties at the tested doses. CONCLUSION: AMG 386 combined with weekly paclitaxel was tolerable, with a manageable and distinct toxicity profile. The data suggest evidence of antitumor activity and a dose-response effect, warranting further studies in ovarian cancer.