Supportive care and quality of life

Nation-wide Questionnaire Study of Cancer Chemotherapy-induced Anemia and Blood Transfusion in Japan

Author(s)：: Ichiro Yoshino¹, Asashi Tanaka², Shigeyoshi Makino², Hiroyuki Kuwano¹,
Yoshihiko Maehara¹, Takayoshi Takahashi², Masahiko Nishiyama¹
Affiliation(s)：: ¹Japan Society of Clinical Oncology, Kyoto, Japan, ² The Japan Society of Transfusion Medicine and Cell Therapy, Tokyo, Japan.

Background: Anemia is one of common adverse effects in anti-cancer chemotherapy. In most developed countries, cancer chemotherapy-induced anemia (CIA) is managed by red blood cell (RBC) transfusion, erythropoiesis-stimulating agents (ESA), or combination of them whereas in Japan, RBC transfusion is the only choice. To investigate an actual situation in management of CIA in Japan, Japan Association of Clinical Oncology and Japan Society of Transfusion Medicine and Cell Therapy conducted a questionnaire-based survey study.
Materials and methods: As primary investigation, 164 hospitals where members affiliated to the societies belonged were inquired of about numbers of cancer chemotherapy, CIA and RBC transfusion in patients with malignancies derived from breast cancer, lung cancer, gastric cancer, colorectal cancer, hepatic cancer, gynecologic cancers, urinary tract cancers and lymphomas during from September 1 to November 30, 2010. As secondary investigation, hemoglobin (Hb) concentration before/after RBC transfusion and adverse effects of blood transfusion were further investigated for randomly selected patients from the cohort of the 1st investigation.
Results: Primary investigation: Sixty five hospitals (39.3%) responded to the questionnaire and data of 107,078 patients with cancers was obtained. Of them, 9,840 patients underwent chemotherapy, and 736 received red blood cell transfusions (7.5%). The blood transfusion rates according to type of malignancy were 1.6 % in breast cancer, 4.1 % in lung cancer, 9.7 % in gastric cancer, 3.5 % in colorectal cancer, 5.1 % in hepatic cancer, 10.3 % in gynecologic cancers, 9.0 % in urinary tract cancers and 7.3 % in lymphomas. A mean amount of transfused blood per patient was 5.9 units, and it was the most as 7.3 units in patients with lymphomas and was the least as 3.9 units in those with hepatic cancer. Patients with CIA with less than hemoglobin (Hb) 10g/dl accounted for 45%, and it was the most in gynecologic cancers (65%) and the least in colorectal cancer (22%). According to a nationwide patient survey conducted by the Ministry of Health, Labour and Welfare, it is estimated that approximately 146,000 units of red blood cells, which account for 2.2% of the annual total supply of red blood cell products, are transfused to cancer patients with CIA yearly. In addition, it is estimated that annually approximately 172,000 cancer patients with CIA, accounting for 40% of patients receiving chemotherapy, have Hb levels below 10 g/dl. Alternative way of care for CIA would be discussed in Japan.
Secondary investigation: In the randomly selected 1,596 patients from the cohort of the primary investigation, 190 (11.9%) had undergone RBC transfusion. Mean Hb concentrations (g/dl) of before/after chemotherapy was 11.6/10.4, and those according to type of malignancy were 11.6/10.4 in breast cancer, 11.8/10.1 in lung cancer, 11.0/9.9 in gastric cancer, 12.0/11.3 in colorectal cancer, 11.7/10.5 in gynecologic cancers, 11.4/9.6 in urinary tract cancers and 11.1/9.6 in lymphomas. Mean Hb concentrations (g/dl) of before/after blood transfusion in the 190 patients was 9.5/6.9, and those according to type of malignancy were 9.5/6.5 in breast cancer, 10.4/7.6 in lung cancer, 9.9/7.4 in gastric cancer, 10.6/7.1 in colorectal cancer, 9.5/7.1 in gynecologic cancers, 9.4/7.2 in urinary tract cancers and 9.5/7.1 in lymphomas. Possible factors affecting blood transfusion included a history of chemotherapy and radiotherapy, as well as the use of platinum agents. Adverse events of blood transfusion accounted for 1.5 %, which was similar to the ratio of adverse events following RBC transfusion in this national survey.
Conclusion: This study is the first nation-wide investigation for CIA in Japan, and revealed an actual situation of CIA and blood transfusion as a supportive care for CIA.

PALO vs GRA for preventing CINV in HEC:A randomized,double-blind,phaseIII　trial

Author(s)：: Yuki Kogure ¹, Naoyuki Nogami ¹, Hironobu Hashimoto ²,
Toshinobu Hayashi ³, Naoko Yasumori ³, Misae Takase ⁴,
Kazuhiko Shibata ⁴, Motohiko Sano ⁵, Norihiro Haga ⁵, Yasunari Mizuno ⁶,
Junichi Shimizu ⁶, Tomoe Yoshizawa ⁷, Takeharu Yamanaka ⁸, Kenichi Suzuki ^{9, 10}, Nobuyuki Yamamoto ⁹
Affiliation(s)：: ¹National Hospital Organization Shikoku Cancer Center, ²National Cancer Center Hospital, ³National Kyushu Cancer Center, ⁴Kouseiren Takaoka Hospital, ⁵Saitama Medical Center, Saitama Medical Univ., ⁶Aichi Cancer Center Hospital, ⁷Tochigi Cancer Center, ⁸Research Center for Innovative Oncology, National Cancer Center Hospital East, ⁹Shizuoka Cancer Center, ¹⁰The Cancer Institute Hospital of JAPANESE FOUNDATION FOR CANCER RESEARCH

Background:
Standard antiemetic care for preventing chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC) is a combination of 5-HT3 receptor antagonist (RA), dexamethasone (DEX), and aprepitant (APR). This study compared the efficacy of two 5-HT3 RAs, palonosetron (PALO) and granisetron (GRA), in the triplet regimen.

Methods:
Patients with a malignant solid tumor who were receiving HEC containing 50 mg/m2 or more cisplatin (CDDP) were enrolled. They were randomly assigned to either Arm A (PALO 0.75 mg, i.v.) or Arm B (GRA 1 mg, i.v.), 30 min before chemotherapy on day 1, both arms with DEX (9.9 mg on day 1 and 6.6 mg on days 2-4, i.v.) and APR (125 mg on day 1 and 80 mg on days 2-3, p.o.). Primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medications) in the overall (0-120 hours) phase. Secondary endpoints included CR in the acute (0-24 h) and delayed (24-120 h) phases, complete control (CC; no emetic episodes, no rescue medications, and no more than mild nausea), total control (TC; no emetic episodes, no rescue medications, and no nausea), time to treatment failure (TTF) and safety. The planned sample size of 840 provided 90% power to detect a 10% improvement in the CR at 0-120 h with two-sided alpha of 0.05. Primary analysis was conducted with exact Cochran-Mantel-Haenszel (CMH) test by use of the stratification factors as strata.

Results:
Between July 2011 and June 2012, 842 patients were enrolled and 827 were evaluable. The median CDDP dose was 76.1 mg/m2 in Arm A and 75.7 mg/m2 in Arm B. Baseline factors were well-balanced. The overall CR rates were 66% in Arm A and 59% in Arm B (P=0.0539). In the delayed phase, Arm A exerted a significantly higher CR rate than Arm B (67% vs. 59%; P=0.0142). The overall CC rates were 64% in Arm A and 56% in Arm B (P=0.0234). The overall TC rates were 48% in Arm A and 41% in Arm B (P=0.0369). The safety profiles of the two arms were similar, and grade 4 treatment-related adverse events were not reported.

Conclusions:
This is the first phase III trial to compare the efficacy of two 5-HT3 RAs within a triplet regimen for preventing CINV due to HEC. Primary endpoint was not met. However, the overall study results have shown the clinical utility of PALO in the triplet regimen. PALO is a more preferable 5-HT3 RA in the triplet regimen than GRA for preventing CINV due to HEC.

Effects of Palonosetron + Dexamethasone(day1) in the prevention of CINV induced by non-AC MEC.

Author(s)：: Y. Sato¹, K. Okita², S. Yuki³, H. Fukushima³, T. Furuhata², Y. Takahashi¹, H. Masuko⁴, K. Hatanaka⁵, H. Isobe⁶, S. Sogabe⁷, K. Sasaki⁸ , M. Nakamura⁹, Y.Ohsaki¹⁰, K. Oba³, Y. Komatsu³
Affiliation(s)：: ¹Hokkaido Cancer Center, ²Sapporo Medical University Hospital, ³Hokkaido University Hospital, ⁴Sapporo-Kosei General Hospital, ⁵Hakodate Municipal Hospital, ⁶KKR Sapporo Medical Center, ⁷Kushiro Rosai Hospital, ⁸Otaru-Ekisaikai Hospital, ⁹Sapporo City General Hospital, ¹⁰Asahikawa Medical University Hospital

[Background] Palonosetron (Palo), a second generation 5HT3 receptor antagonist, is recommended for the prevention of chemotherapy induced nausea and vomiting (CINV) at the time of the moderately emetogenic chemotherapy (MEC) in international antiemetic guidelines such as MASCC, ASCO and NCCN.
However, administration schedule of steroids which are also recommended in the combination has been established based on the data obtained with the first generation 5-HT3 receptor antagonists. Literature reporting the appropriate administration period of steroids when used with Palo is limited, and there have not yet been any reports worldwide, when against non-AC MEC.
The purpose of this study was to confirm the non-inferiority of Palo + Dexamethason (Dex) day 1 single administration against Palo + Dex days 1-3 administration, the current standard therapy for CINV in non-AC MEC.
[Method] This study was carried out as a multicenter, randomized non-inferiority phase Ⅲ study.
Patients receiving non-AC MEC as an initial chemotherapy were enrolled and randomized to either a group which was administered Palo (0.75 mg, IV) and Dex (9.9 mg, IV) prior to chemotherapy(PALO+DEX day1), or a group which was administered similar regimen on day 1 with additional administration of Dex (8 mg, IV or PO) in day 2-3 (PALO+DEX day1-3) by minimization method.
Primary endpoint was complete response (CR; no emesis and no rescue medication) during 5 days after chemotherapy administration.
[Results] Analysis was conducted in 305 patients enrolled from April, 2011 to March, 2013. As for the non-AC MEC regimens, 72.8% were oxaliplatin based, 13.4% were irinotecan based, 12.1% were carboplatin based, and 1.7% used other agents.
Non-inferiority was demonstrated in the overall CR rate, 68.2% in PALO+DEX day1 group (n=151) and 64.7% in PALO+DEX day1-3 group (n=154).
There also were no differences between the groups in the acute phase CR rate, and delayed phase CR rate.
[Conclusion] Non-inferiority of PALO+DEX day1 therapy against the standard PALO+DEX day1-3 therapy for the prevention of CINV in non-AC MEC was demonstrated in this study.
No similar reports focusing on non-AC MEC has been available up to now. In conclusion, the administration of day 2-3 Dex can be omitted when used with Palo for the prevention of CINV inpatients receiving non-AC MEC.

Active palliation and new treatment strategies for malignant ascites using KM-CART

Author(s)：: Keisuke Matsusaki ¹⁾ , Keiichiro Ohta ²⁾, Akitaka Yoshizawa ¹⁾
Affiliation(s)：: 1)Kanamecho Hospital, Ascites Treatment Center
2)Shonan Kamakura General Hospital, Oncology Center

Objective: By inducing symptoms such as severe abdominal fullness and respiratory discomfort, and because it is difficult to treat with opioids and leads to discontinuation of cancer therapy, the massive ascites associated with peritonitis carcinomatosa not only markedly reduces patients' activities of daily living (ADL), it can also sap them of their will to survive. Cell-free and concentrated ascites reinfusion therapy (CART) was approved in 1981 as a treatment method for refractory ascites that is covered by health insurance; however, because malignant ascites caused the clog of membrane at an early stage due to their various properties, this treatment method has yet to be adopted. Since 2009, we have actively implemented the originally developed KM-CART system, which was modified from CART. It is easier to use and can be applied for massive malignant ascites. KM-CART is performed by removing the entire volume of ascitic fluid (maximum, 27 L) and administering the recovered autologous proteins into blood vessels by infusion. The effectiveness of KM-CART in alleviating symptoms and the potential application of massive amounts of cancer cells recovered from the membrane washing fluid in personalized medicine are hereby reported.
Methods and Results: A total of 1037 patients, including 208 ovarian cancer patients, 151 gastric cancer patients, 129 colon cancer patients, and 549 patients with other disorders, underwent KM-CART between February 2009 and August 2013. Ascitic fluid was removed to the greatest extent possible (0.8–27.0 L; mean, 6.8 L), and removal took between 5 and 221 min (mean, 64 min). The mean processing rate was 10.2 min/L, and between 100 and 2000 mL (mean, 600 mL) of filtered concentrate was created and administered by intravenous infusion. Side effects consisted of only mild fever, with no serious side effects observed. In all 87 patients for whom a questionnaire survey could be conducted on both the day before and the day after KM-CART, symptom scores improved for 10 items, including abdominal fullness, respiratory discomfort, decreased appetite and gait impairment. Due to alleviation of edema, mean lower leg circumference also decreased by 2.8 cm, indicating the effectiveness of KM-CART in improving the ADL of patients. In addition, some patients resumed chemotherapy as a result of regaining the motivation to fight disease. These patients were able to transition to their homes over the long-term. Furthermore, 2.4105 cancer cells were recovered from the membrane filter washing fluid in each of 14 patients with ovarian cancer or other disorders, and these cells were able to be used for dendritic cell (DC) vaccine therapy. Moreover, many viable cells survived and formed spheroids on the day after culture, and active proliferation was observed on day 8. The combination with KM-CART performed every two weeks for massive ascites that developed after 42 courses of chemotherapy enabled five months of recuperation at home for a patient with colon cancer who was able to continue vaccine use.
Conclusion: The KM-CART system was considered easy to use and very safe, and the recovery of large volumes of autologous proteins was thought to have improved general status, nutrition, and immune status, as well as subjective symptoms, and to have led to more effective alleviation of symptoms. In addition, the recovered cancer cells were able to be used for drug sensitivity tests and immune cell therapy, indicating the potential for new treatment strategies for malignant ascites in the future.

A Study of Self-care Support for Oral Health Care of Chemotherapy Treated Patient

Author(s)：: Aki Matsumaru, Kayoko Makino, Yukio Sakata, Noriyosi Takahashi, Hideyuki Minamida, Kazuteru Hatanaka
Affiliation(s)：: Hakodate Munucipal Hospital

Purpose: Since fiscal 2011, the dental surgery of our hospital has intervened to perform the oral care before the first chemotherapy treatment and in fiscal 2011, the consultation rate of the dental surgery was 45% and the onset rate of the oral mucositis was 41%. Since fiscal 2012, for the critical prevention of the oral mucositis, the nurses have continued to perform the self-care support of the patients regardless of the PS after the dental surgery consultation. We have investigated the current situation of the subsequent occurrences of the oral mucositis and considered the future tasks.

Subjects: 166 patients to whom the first chemotherapy was performed from 2011 to 2013.
(78 patients from June 2011 to September 2012, 88 patients from October 2012 to March 2013)

Methods: The onset rates of the oral mucositis and the consultation rates of the dental surgery before and after the nursing intervention were compared and considered.
As ethical considerations, the investigation and consideration was performed not to identify the personal information the patients retrospectively.
As the evaluation method of the oral mucositis,we used CTCAE Ver.4.

Results: Before and after the self-care support, the consultation rate of the dental surgery before chemotherapy increased from 45% to 94%, the onset rate of the oral mucositis for Grade 1 or more decreased from 41% to 9%, that for Grade 2 or more decreased from 21% to 2%, and the onset rate of the candidal vaginitis also decreased from 9% to 1%.
In addition, the 50% and more of the both oral mucositis onset before and after the self-care support was the regimen including fluorouracil and capecitabine.

Considerations: The onset rate of the oral mucositiswas decreased by performing the self-care support of the patients regardless of the PS. Some reasons would be considered to decrease the oral mucositis onset that the satisfactory oral mucosa environment could be prepared before the chemotherapy as the consultation rate of the dental surgery before the chemotherapy increased and the patients themselves could obtain the self-care capability to keep the oral environment as the nurses continued the self-care support.
In addition, since the onset rate of the oral mucositis of the regimen including fluorouracil and capecitabineis high, both medicines are used for a long term, and they can be the cause to significantly decrease the QOL of the patients, the care should be performed with special caution. While the ambulatory chemotherapy currently increases, it is considered that the important task is to support to keep the self-care capability of the patients and family at home.

Conclusions: It is possible to continue the treatment holding the QOL against the chemotherapy treated patients by performing the self-care support against oral mucositis.

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