COOKING ALL THE WAY

Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer
Zhiqiang Meng, MD, PhD 1, Peiying Yang, PhD 2, Yehua Shen, MD 1, Wenying Bei, RN 1, Ying Zhang, RN 1, Yongqian Ge, MD 1, Robert A. Newman, PhD 3 a, Lorenzo Cohen, PhD 2 4 *, Luming Liu, MD, PhD 1 *, Bob Thornton, MPH 2 b, David Z. Chang, PhD 5, Zongxing Liao, MD 6, Razelle Kurzrock, MD 7
1International Center of Integrative Oncology, Fudan University Cancer Hospital, Shanghai, China
2The Integrative Medicine Program, Department of General Oncology, The University of Texas M. D. Anderson Cancer, Houston, Texas
3Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
4Department of Behavioral Science, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
5Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
6Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
7Department of Investigational Cancer Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
email: Luming Liu (llm1010@163.com)


*Correspondence to Lorenzo Cohen, Department of Behavioral Science, Unit 145, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030

*Correspondence to Luming Liu, International Center of Integrative Oncology, Fudan University Cancer Hospital, 270 Dong An Road, Shanghai, 200032, China

aCurrent address: New Chapter Inc, Brattleboro, Vermont

bCurrent address: Merck & Co, Inc., Whitehouse Station, New Jersey
Fax: (011) 862164437657

Funded by:
 National Cancer Institute; Grant Number: CA108084, CA12153031
Keywords
pancreatic cancer • hepatocellular cancer • nonsmall cell lung cancer • phase 1 • traditional Chinese medicine

Abstract

BACKGROUND:
Huachansu, a Chinese medicine that comes from dried toad venom from the skin glands of Bufo gargarizans or B. melanostictus, has been used in the treatment of various cancers in China. The authors conducted a pilot study, using a phase 1 trial design, of huachansu in patients with advanced cancer.

METHODS:
Huachansu was administered intravenously for 14 days followed by 7 days off (1 cycle). Without significant adverse events or progressive disease, treatment continued beyond 2 cycles. The dose of huachansu was escalated as follows with 3 patients per cohort: 10 (level 1), 20 (level 2), 40 (level 3), 60 (level 4), and 90 (level 5) mL/m2.

RESULTS:
Fifteen patients (hepatocellular cancer, n = 11; nonsmall cell lung cancer, n = 2; pancreatic cancer, n = 2) were enrolled in the trial, and no dose-limiting toxicities (DLTs) were found. Eleven patients had no drug-related toxicity greater than grade 1. Six (40%) had stable disease (median duration, 6.0 months; range, 3.5-11.1 months). One of these patients (with hepatocellular cancer) had 20% regression (duration, 11 months) (dose level 1). Quality of life improved for patients with stable disease. Plasma bufalin concentration reached maximal levels at the end of the 2-hour infusion and was proportional to the amount of drug being administered (0.81-3.38 ng/mL).

CONCLUSIONS:
No DLT was observed with the use of huachansu at doses up to 8× higher than typically used in China. Six patients had prolonged stable disease or minor tumor shrinkage. Cancer 2009. © 2009 American Cancer Society.

The Depressing Thing About Cancer

Sara Hartley
Medical Writer, MDLinx Oncology

It has long been known that individuals with cancer are at much greater risk for depression, anxiety and other mood disorders compared to healthy individuals. Studies suggest that at least 25% of patients hospitalized for cancer meet criteria for major depression, and the prevalence is even higher for those with breast, lung, or pancreatic cancers. 

Co-morbid depression is strongly associated with treatment noncompliance and decreased survivorship in cancer patients—underscoring the profound clinical significance of this condition. A number of factors are speculated to play a role in cancer-related depression, including subjective disease awareness, side effects of chemotherapy, and direct biological effects of the tumor. However, the relative contributions of each of these factors in the pathogenesis of cancer-associated depression remain largely unknown. 

Now researchers at the University of Chicago report some of the first evidence to show that peripheral tumors secrete substances into the bloodstream that act on the mood controlling centers in the brain. The researchers used a drug to induce mammary tumors in rats and then studied their behavior before and after tumor development. Compared to controls and drug-treated rats prior to tumor development, rats with mammary tumors exhibited high levels of depressive behavior, such as decreased motivation to escape a swimming test and reduced interest in drinking sugar water. Moreover, the tumor-bearing rats had significantly higher levels of certain cytokines (e.g., IL-1beta, IL-6) in the blood and brain, and impaired gene expression in the hippocampus—a major emotion-regulating center in the brain.

Together, these findings strongly suggest that tumor cells can secrete humoral factors that influence mood, and argue that depression should be added to the list of paraneoplastic syndromes.

Source

Pyter LM, Pineros V, Galang JA, et al. Peripheral tumors induce depressive-like behaviors and cytokine production and alter the hypothalamic-pituitary-adrenal axis regulation. Proc Natl Acad Sci. USA. 2009;106(22):9069-74.

BELIEVE IT OR NOT, ECF IS DEAD

Thromboembolism in Patients With Advanced Gastroesophageal Cancer Treated With Anthracycline, Platinum, and Fluoropyrimidine Combination Chemotherapy: A Report From the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group

Naureen Starling, Sheela Rao, David Cunningham, Timothy Iveson, Marianne Nicolson, Fareeda Coxon, Gary Middleton, Francis Daniel, Jacqueline Oates, Andrew Richard Norman 

Originally published as JCO Early Release 10.1200/JCO.2008.19.4274 on April 27 2009


Journal of Clinical Oncology, Vol 27, No 23 (August 10), 2009: pp. 3786-3793
© 2009 American Society of Clinical Oncology.

From the Royal Marsden Hospital National Health Service Foundation Trust, Surrey and London; Southampton University Hospital National Health Service Trust, Southampton; Salisbury Hospital National Health Service Foundation Trust, Salisbury; Oncology–Anchor Unit, Aberdeen Royal Infirmary, Aberdeen; Northern Centre for Cancer Treatment, Newcastle-Upon-Tyne; St Luke's Cancer Centre, Guildford; and Plymouth Oncology Centre, Plymouth, United Kingdom. 

Corresponding author: David Cunningham, MD, FRCP, Department of Medicine, Royal Marsden Hospital, Downs Rd, Sutton, Surrey, SM2 5PT United Kingdom; e-mail: david.cunningham@rmh.nhs.uk.

Purpose Data concerning the prevalence of and outcomes related to thromboembolic events (TEs) in patients with advanced gastroesophageal cancer who are undergoing chemotherapy are limited. 

Patients and Methods This was a prospective, exploratory analysis of TEs in a randomized, controlled trial of 964 patients recruited between 2000 and 2005 and treated with epirubicin/platinum/fluoropyrimidine combination chemotherapy for advanced/locally advanced gastroesophageal cancer. Regimens were epirubicin (E), cisplatin (C), fluorouracil (F; ECF); E, C, capecitabine (X; ECX); E, F, oxaliplatin (O; EOF); and EOX. Continuously infused F was administered via a central venous access device (CVAD) with 1 mg of warfarin for thromboprophylaxis. The principal outcome was the incidence of TEs (venous and arterial) in the whole treated patient cohort, according to chemotherapy, associated with CVADs and TE-related prognoses. 

Results The incidences of any, of venous, and of arterial TEs among 964 treated patients were 12.1% (95% CI, 10.7 to 14.3), 10.1% (95% CI, 8.3 to 12.3), and 2.2% (95% CI, 1.4 to 3.4) respectively. There were fewer TEs in the O compared with the cisplatin groups (EOF/EOX v ECF/ECX: 7.6% v 15.1%; P = .0003). C was identified as a risk factor for TE in multivariate analysis (hazard ratio [HR], 0.51; 95% CI, 0.34 to 0.76; P = .001). There was no difference in the incidence of TEs for the F group compared with the capecitabine groups. The incidence of CVAD-related thrombosis was 7.0% (ECF/EOF arms). Overall survival was worse for patients who experienced TEs versus no TEs (median survival, 7.4 v 10.5 months; HR, 0.8; 95% CI, 0.64 to 0.99; P = .043). 

Conclusion This analysis has prospectively quantified the incidence/pattern of TEs among patients with advanced gastroesophageal cancer who were treated with four triplet regimens, has demonstrated a differential thrombogenic effect according to platinum use, and has noted a poorer outcome associated with TE during treatment. Chemotherapy-related TE should contribute to the risk/benefit assessment of treatment. 

Supported in part by Hoffmann-La Roche Inc and sanofi-aventis. 

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. 

Clinical trial information can be found for the following: NCT51678883. 

The authors acknowledge NHS funding to the NIHR Biomedical Research Centre.