Background: For patients (pts) with cancer, treatment with cytotoxic chemotherapy is associated with a variety of treatment-related symptoms including nausea, vomiting, diarrhea and constipation. Often the ability to manage these symptoms when they occur is the difference between completion of chemotherapy and early discontinuation. The first weeks of treatment are critical for understanding the pts’ acute experience with chemotherapy. The objective of this study is to longitudinally evaluate treatment-related symptoms and associated treatment burden among chemotherapy pts through a real-world electronic remote symptom monitoring system. Methods: Pts treated with chemotherapy in U.S. academic cancer centers were enrolled in Carevive’s Patient Reported Outcomes Mobile Platform (Carevive PROmpt®) between September 2020 and Dec 2023, with 3 month median follow-up. A total of 476 pts were enrolled, across early (81%) and late (19%) stage disease. Weekly PRO-CTCAE-derived surveys assessed severity, frequency, and interference for 16 symptoms often associated with cancer treatment: anxiety, constipation, cough, decreased appetite, diarrhea, fatigue, general pain, insomnia, mouth/throat sores, muscle pain, nausea, numbness and tingling, rash, sadness, shortness of breath, and vomiting. The GP5 assessed weekly overall bother with the side effects of treatment. Questionnaires were administered weekly starting at treatment initiation. Results: The mean age of chemotherapy pts was 67.3 (SD = 13.2) years, with 75% female, and 20% African American. At treatment initiation, 302 pts reported symptoms by PRO-CTCAE, and 100 completed the GP5. At week 1, constipation, general pain (GP), nausea, numbness/tingling (N/T), and shortness of breath were experienced by 20-25% of pts. Over the first 4 weeks of treatment, pts reported an increase in constipation, decreased appetite, diarrhea, and nausea at week 2, with a return to week 1 frequency over the remaining weeks. Diarrhea, however, remained elevated. While week 1 capture rates were lower, patterns for treatment bother were similar. At week 1, 34% of pts reported being bothered at least “Somewhat” by the side effects of treatment. This increased to 48% at week 2, but returned to near the week 1 frequency over the remaining weeks. Conclusions: For remote-monitored pts in this real-world data set treated with chemotherapy both alone and in combination, the most frequent symptoms at the start of treatment were nausea, GP, and N/T. The frequency of pts with GP and N/T did not change over the course of treatment suggesting their possible presence prior to the observed regimen. Increases in chemotherapy-related symptoms show the importance of ongoing assessment over the first 4 weeks of treatment, ideally with feedback to treating physicians and concomitant symptom management to optimize successful chemotherapy completion.