Phase I clinical and pharmacokinetic study of PM01183 (a tetrahydroisoquinoline, Lurbinectedin) in combination with gemcitabine in patients with advanced solid tumors

Background To determine the recommended dose (RD) of a combination of PM01183 and gemcitabine in patients with advanced solid tumors. Methods Forty-five patients received escalating doses of PM01183/gemcitabine on Days 1 and 8 every 3 weeks (d1,8 q3wk) following a standard 3 + 3 design. Results PM01183 3.5 mg flat dose (FD)/gemcitabine 1000 mg/m(2) was the highest dose level tested. Dose-limiting toxicities (DLTs) were mostly hematological and resulted in the expansion of a lower dose level (PM01183 3.5 mg FD/gemcitabine 800 mg/m(2)); 19 patients at this dose level were evaluable but >30% had DLT and >20% had febrile neutropenia. No DLT was observed in 11 patients treated at PM01183 3.0 mg FD/gemcitabine 800 mg/m(2), which was defined as the RD. This regimen was feasible and tolerable with manageable toxicity; mainly grade 3/4 myelosuppression. Non-hematological toxicity comprised fatigue, nausea, vomiting, and transaminases increases. Fifteen (33%) patients received ≥6 cycles with no cumulative hematological toxicity. Pharmacokinetic analysis showed no evidence of drug-drug interaction. Nine of 38 patients had response as per RECIST (complete [3%] and partial [21%]), for an overall response rate (ORR) of 24% (95% Confidence Interval [CI] 12-40%). Eleven patients (29%) had disease stabilization ≥4 months. Responses were durable (median of 8.5 months): overall median progression-free survival (PFS) was 4.2 months (95% CI, 2.7-6.5 months). Conclusions The RD for this combination is PM01183 3.0 mg FD (or 1.6 mg/m(2))/gemcitabine 800 mg/m(2) d1,8 q3wk. This schedule is well tolerated and has antitumor activity in several advanced solid tumor types

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Preditores de soropositividade para HIV em indivíduos não abusadores de drogas que buscam centros de testagem e aconselhamento de Porto Alegre, Rio Grande do Sul, Brasil Predictors of HIV seropositive status in non-IV drug users at testing and counseling centers in Porto Alegre, Rio Grande do Sul, Brazil

Este estudo descreve comportamentos de risco para HIV, obtidos através de questionário, em 570 indivíduos de Porto Alegre que não usavam drogas regularmente. A idade média foi 30,3, 51,1 % eram homens, e a maioria tinha baixa renda (59,1%). A soropositividade foi de 9,9% (13,1% entre homens e 6,9% entre mulheres), associada a sexo masculino, ter mais de 30 anos e baixa renda. Mulheres reportaram mais sexo desprotegido (86,4%) do que homens (74,4%) e mais sexo com usuários de droga injetável (11,6% versus 2,1%); homens relataram mais sexo homossexual desprotegido (18,7% versus 1,4%) e mais relações com profissionais de sexo (19,0% versus 0,4%). Não houve associação entre uso eventual de drogas e soropositividade. A idade associada à soropositividade confirma achados anteriores, indicando maior exposição a riscos durante a vida. O estudo confirma a pauperização da epidemia, com indivíduos pobres apresentando maior soropositividade. Homens e mulheres apresentaram diferentes comportamentos associados à soropositividade, confirmando a necessidade de prevenção específica e distinta para cada grupo.<br>This study describes HIV-related behaviors recorded through a questionnaire applied to 570 individuals in Porto Alegre, Rio Grande do Sul, Brazil, who were not regular drug users. Mean age was 30.3 years, 51.1 % were male, and most were low-income (59.1%). The HIV seropositive rate was 9.9% (13.1% for males, 6.9% for females), and there was a positive association with male gender, age over 30 years, and low income. Women reported more unprotected sex (86.4%) than men (74.4%) and more sex involving drugs (11.6% vs. 2.1%); men reported more unprotected homosexual sex (18.7% vs. 1.4%) and more sex with sex workers (19.0% vs. 0.4%). There was no association between sporadic drug use and seropositive status. The association between age and seropositive status confirms previous findings, indicating more lifetime risk exposure. The study confirms the so-called pauperization of the epidemic, with poor individuals showing a higher seropositive rate. Males and females showed different behaviors associated with seropositive status, confirming the need for specific and differentiated preventive strategies for each group