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First-line palliative chemotherapy regimens in advanced pancreatic adenocarcinoma include triplet chemotherapy with 5-fluorouracil, oxaliplatin, and irinotecan, and the doublet of nab-paclitaxel plus gemcitabine. Use of triplet chemotherapy in real-world populations is limited by tolerability and nab-paclitaxel is not universally available. Regimens using the combination of cisplatin, capecitabine, gemcitabine, and either epirubicin or docetaxel may be better tolerated, more widely available, and similarly effective, but no published real-world data exist.A retrospective cohort review of patients with metastatic or unresectable locally advanced pancreatic adenocarcinoma treated with first-line palliative cisplatin, capecitabine, gemcitabine, and either epirubicin or docetaxel chemotherapy at Auckland City Hospital between July 1, 2013 and July 30, 2020. The primary outcome was overall survival (OS). Secondary outcomes were rates of grade 3 or 4 hematological toxicity, rate of febrile neutropenia, number of cycles received, and reasons for discontinuation.Eighty-eight patients were included. Median age was 66 years (range 39-79), 28.4% had unresectable, locally advanced disease and 71.6% metastatic disease. Median OS was 8.5 months. Patients stopped treatment due to disease progression (53.4%), completing 12 cycles (19.3%), or toxicity (10.2%). Grade 4 neutropenia was experienced by 21.6%; 10.2% had febrile neutropenia. There were four treatment-related deaths.This retrospective study in a real-world population demonstrates that chemotherapy with cisplatin, capecitabine, and gemcitabine with epirubicin (PEXG) or docetaxel (PDXG) had similar effectiveness to more commonly used combination regimens. PDXG/PEXG are viable alternatives to nab-paclitaxel plus gemcitabine in countries that have restricted drug funding.

Aims Serum carcinoembryonic antigen (CEA) is used to detect relapses from colon cancer following initial surgical or adjuvant treatment. There are little data on transient elevations of CEA while receiving chemotherapy in the adjuvant setting. We aimed to review patterns of change in CEA levels while receiving adjuvant chemotherapy and investigate associations between transient rises and patient survival. Methods A retrospective review of patients in Auckland with a new diagnosis of colon cancer in 2001 or 2005 was performed and CEA values were collected. Three patient groups were defined: no increase in CEA; transient elevation in CEA; and persistent elevation in CEA. Kaplan–Meier methods were used to estimate 5-year survival; Cox regression and log-rank P-values were used to compare survival. Results Sixty-one patients with stage II or III disease who had received adjuvant chemotherapy had sufficient CEA data to be included in the analysis. Patients were followed up for a minimum of 7.4 years (or death). The 5-year overall survival was higher in the transient elevation in CEA group 95.0% and the no increase in CEA group 85.2% compared with the persistent elevation in CEA group 42.9%. There was no statistically significant difference in overall survival between the transient elevation group and the no increase group (P = 0.2). Conclusions The group with a transient elevation in CEA during adjuvant chemotherapy did not have a poorer prognosis compared with the group that had no increase in CEA. This will be further examined in a population-based New Zealand-wide study of colorectal cancer diagnosis, treatment and outcome.

In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial.

Aim: The purpose of the study was to determine the feasibility and validity of using health-related quality of life (HRQL) and patient benefit as outcome measures in a phase II trial of octreotide long acting release (LAR) for hepatocellular carcinoma (HCC); and, to determine aspects of HRQL that were most impaired and aspects that changed. Methods: Sixty-three patients with advanced HCC were treated with octreotide LAR. HRQL was assessed monthly with the Functional Assessment of Cancer Therapy – Hepatobiliary Questionnaire (FACT-Hep) and the Patient Disease and Treatment Assessment Form (Patient DATA Form). Benefit was assessed directly by asking subjects at 1 month about change from baseline using the Patient Benefit Form. Convergent, discriminative and predictive validity were assessed by testing a priori hypotheses. Results: Seventy-three percent completed a baseline assessment of HRQL. Compliance decreased over time. Fatigue, energy, anxiety, pain, insomnia, and emotional well-being were the most impaired aspects of HRQL on the Patient DATA Form. Convergent validity was supported by 52 of 57 hypothesized correlations. Predictive validity was supported by associations between survival and four aspects of HRQL. Patients' direct assessments of benefit for common symptoms were moderately associated with changes in their scores on the Patient DATA Form. Conclusion: Use of the FACT Hep and Patient DATA Form is feasible in trials of advanced HCC. The validity of the direct measure of patient benefit was questionable, despite its intuitive attraction. Fatigue, anxiety, insomnia, and impaired emotional well-being were prominent, are probably under-recognized in practice, and are worthy of future research.

Background: This dose escalation study assessed feasibility of a totally oral chemotherapy regimen using cyclophosphamide and capecitabine. The rationale for this combination was based on the observation that preclinical models of cyclophosphamide up-regulated tumor thymidine phosphorylase and increased the activation of capecitabine. Methods: Eligible patients with advanced cancer were treated with oral cyclophosphamide and capecitabine on a 28-day cycle. If no dose limiting toxicities (DLT) were encountered during the first two treatment cycles, the next patient group was assigned to the next highest dose level until the maximum tolerable dose (MTD) was determined. Results: Twenty-seven patients entered treatment. The majority of non-DLT were grades 1 and 2. DLT experienced in the first 8-week observation period were grade 3 diarrhea (one patient, level III) and grade 3 emesis (two patients, level V). MTD was observed at level 5, 1331 mg/m2/day capecitabine days 1–28 with 125 mg/m2/day cyclophosphamide days 1–14 of the 28-day cycle. The recommended phase II dose is therefore 1331 mg/m2/day capecitabine with 100 mg/m2/day cyclophosphamide. The best response evaluation showed four partial responses (breast, colon, ovary and pancreas). Conclusion: Cyclophosphamide and capecitabine can be combined at their full oral single agent dose with promising tolerability and activity.

Serum carcinoembryonic antigen (CEA) is used to detect relapses from colon cancer following initial surgical or adjuvant treatment. There are little data on transient elevations of CEA while receiving chemotherapy in the adjuvant setting. We aimed to review patterns of change in CEA levels while receiving adjuvant chemotherapy and investigate associations between transient rises and patient survival.A retrospective review of patients in Auckland with a new diagnosis of colon cancer in 2001 or 2005 was performed and CEA values were collected. Three patient groups were defined: no increase in CEA; transient elevation in CEA; and persistent elevation in CEA. Kaplan-Meier methods were used to estimate 5-year survival; Cox regression and log-rank P-values were used to compare survival.Sixty-one patients with stage II or III disease who had received adjuvant chemotherapy had sufficient CEA data to be included in the analysis. Patients were followed up for a minimum of 7.4 years (or death). The 5-year overall survival was higher in the transient elevation in CEA group 95.0% and the no increase in CEA group 85.2% compared with the persistent elevation in CEA group 42.9%. There was no statistically significant difference in overall survival between the transient elevation group and the no increase group (P = 0.2).The group with a transient elevation in CEA during adjuvant chemotherapy did not have a poorer prognosis compared with the group that had no increase in CEA. This will be further examined in a population-based New Zealand-wide study of colorectal cancer diagnosis, treatment and outcome.