Japanese Journal of Clinical Oncology Advance Access originally published online on May 31, 2005
Japanese Journal of Clinical Oncology 2005 35(6):349-352; doi:10.1093/jjco/hyi093
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© 2005 Foundation for Promotion of Cancer Research
Case Report |
A Long-term Survival Case of Small Cell Lung Cancer in an HIV-infected Patient
Division of Respiratory Disease, Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
For reprints and all correspondence: Tetsuro Kato, Division of Respiratory Disease, Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22, Hon-Komagome, Bunkyo-ku, Tokyo, 113-8677 Japan. E-mail: katetsu{at}av5.mopera.ne.jp
Received July 26, 2004; accepted February 15, 2005
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Abstract |
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 TOP Abstract INTRODUCTIONCASE REPORTDISCUSSIONReferences |
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We report a case of small cell lung cancer in a patient with human immunodeficiency virus (HIV) infection. The patient was a 51-year-old man diagnosed 8 years previously as seropositive for HIV, who was admitted to our hospital for re-evaluation of antiretroviral medications due to multidrug resistance. Chest radiograph revealed an abnormal hilar shadow subsequently confirmed to be small cell lung cancer. He received chemotherapy concurrently with highly active antiretroviral therapy (HAART), and lived for 14 months after the diagnosis. The prognosis of lung cancer in HIV-seropositive patients is very poor, and adverse effects of chemotherapy occur more frequently than in other patients. However, the simultaneous antiretroviral agents and combination chemotherapy was successful. Such treatment may be effective despite an otherwise poor prognosis, including HIV infection.
Key Words: small cell lung cancer • human immunodeficiency virus (HIV) • highly active antiretroviral therapy (HAART)
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INTRODUCTION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONReferences |
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Besides some opportunistic infections, malignant disorders occur in human immunodeficiency virus (HIV)-infected patients, including acquired immunodeficiency syndrome (AIDS)-related malignancies and non-AIDS-defining malignancies. Since HIV infection can now be well controlled by highly active antiretroviral therapy (HAART), the incidence and mortality of malignant disorders have increased in HIV-infected patients (1–3). The prognosis of such diseases is very poor in general, and chemotherapy is very difficult because adverse effects occur more frequently. In this report, we present a case of small cell lung cancer in an HIV-infected patient who received systemic chemotherapy concurrently with HAART, and survived for 14 months after the diagnosis. This relatively long-term survival may be attributed to three factors: HIV infection was well controlled, there were no opportunistic infections and adverse effects did not occur during chemotherapy. HAART increases the feasibility of effective treatment without serious adverse effects, thus it provides strong support for the management of small cell lung cancer in HIV-infected patients.
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CASE REPORT |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONReferences |
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A 51-year-old man seropositive for HIV since 8 years previously was admitted to our hospital in August 2002 to receive a modified antiretroviral drug treatment because of multidrug resistance. The patient had started to receive antiretroviral treatment in 1994 with three subsequent changes in the drug regimen. An abnormal shadow was found in a chest radiograph obtained on admission. No respiratory symptoms were observed and his performance status was zero at presentation. Fine crepitation was apparent by auscultation at the bases of both lungs on examination.
Laboratory findings on admission (Table 1) included increased neuron-specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP). The CD4(+) lymphocyte count was 324/µl, and HIV-RNA PCR was 4.1 x 104 copies/ml.
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Chest radiograph (Fig. 1) and computed tomography of the chest (Fig. 2) and abdomen revealed a left hilar mass and enlargement of the left adrenal gland, respectively. Fiberoptic bronchoscopy showed a whitish left hilar tumor, and examination of a biopsy specimen revealed small cell carcinoma. No evidence of brain or bone metastasis was detected by systemic survey. The diagnosis of extensive stage disease of small cell lung cancer was confirmed.
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The patient began a new HAART regimen, consisting of 250 mg of didanosine, 600 mg of abacavir sulfate, 600 mg of efavirenz, 2400 mg of amprenavir and 200 mg of ritonavir in September 2002. Systemic chemotherapy included 30 mg/m2 of cisplatin and 60 mg/m2 of irinotecan hydrochloride weekly for 3 weeks of a 4 week cycle administered 2 weeks later. Although the lesion was reduced by three courses of this treatment [partial response (PR), in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)] (Fig. 3), the cancer relapsed with multiple brain, skin, liver and bone lesions 2 months after the completion of chemotherapy (Figs 4 and 5). Whole brain irradiation (40 Gy), and four courses of amrubicin hydrochloride (35 mg/m2) for three consecutive days of a 3 week cycle decreased the lesions (PR by RECIST), but the cancer relapsed again in brain, bone, liver, adrenal gland and skin.
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Although two courses of carboplatin (area under the concentration–time curve of 5 mg/min/ml) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 were administered as third-line treatment, lesions were refractory [progressive disease (PD) by RECIST].
Before the fourth-line treatment was planned, the patient's level of consciousness had deteriorated because of the re-growth of the brain metastasis. We changed the level of therapy to best supportive care. The patient died in October 2003 due to cancer progression. Post-mortem examination revealed multiple metastatic small cell cancer lesions, but no opportunistic infections.
We monitored NSE and ProGRP as tumor markers as well as HIV load and CD4(+) lymphocyte count during chemotherapy (Fig. 6). Tumor markers decreased in parallel with the degree of the response to chemotherapy. No severe CD4(+) lymphocytopenia was seen and the HIV load could be kept under 50 copies/ml by administration of HAART throughout the course.
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DISCUSSION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONReferences |
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Non-Hodgkin's lymphoma, Kaposi's sarcoma and invasive cervical cancer are common HIV-related malignancies, but non-HIV-defining malignancies, including colon, stomach and lung cancers, have increased in the HAART era (2,3). Lung cancer is the most common solid cancer, because HIV patients are more often smokers, which is the strongest risk factor for lung cancer (3). Parker et al. reported that the incidence of primary lung cancer is increased by 6.5-fold in HIV-infected patients (4). It is because immune surveillance is impaired in their lungs(5).
The clinical courses of lung cancer in HIV-infected patients are generally more aggressive than in non-HIV patients. Tirelli et al. reported that the median overall survival in patients with HIV was significantly shorter than in those without (6). Tammemagi et al. indicated that the co-morbidity of HIV infections reduced lung cancer survival (7). A few cases of small cell lung cancer in HIV-infected patients have been reported so far, and the prognosis of all cases was extremely poor (8).
In our case, we administered systemic chemotherapy concurrently with HAART. It is well known that hematopoiesis is compromised in HIV infection (9). Therefore, myelosuppression due to chemotherapy may be excessive, but there are reports of successful chemotherapy with concurrent antiretroviral therapy for HIV-related lymphoma (10). We used a similar method and could continue nine courses of chemotherapy without excessive adverse effects or opportunistic infections. CD4(+) lymphocyte count and HIV load were well controlled throughout the course.
However, one needs to consider the interaction between anticancer and antiretroviral drugs. Protease inhibitors, such as ritonavir or lopinavir/ritonavir, strongly inhibit the drug-metabolizing enzyme cytochrome P450 3A4 and thus increase the serum concentration of anticancer drugs in concurrent use (11). Specifically, toxicity of vincristine and paclitaxel, that are metabolized by cytochrome P450, have a risk of increase due to higher serum concentration. The combination of anticancer drugs and HAART requires such careful considerations of drug properties.
Our patient's long-term survival was based on good performance status, controlled HIV load, absence of opportunistic infections and the effectiveness of amrubicin hydrochloride, a new drug for small cell lung cancer. Amrubicin hydrochloride is a completely synthetic anthracycline derivative. For previously untreated small cell lung cancer, the response rate with amrubicin was 78.8%, and the median survival time was 11.7 months (12). This agent is also effective for relapsed small cell lung cancer.
In the era of HAART, the incidence and mortality of malignant disorders in HIV-infected patients is increasing. The management of such cases is complicated and difficult. Therefore, the relatively long survival of our patient is instructive. By controlling HIV infection with HAART, chemotherapy could be optimized without excessive adverse effects; this approach can prolong survival in small cell lung cancer occurring in HIV-infected patients.
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References |
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1 Bower M, Powles T, Nelson M, Shah P, Cox S, Mandelia S, et al. HIV-related lung cancer in the era of highly active antiretroviral therapy. AIDS 2003;17:371–5.[CrossRef][Web of Science][Medline]
2 Bonnet F, Lewden C, May T, Heripret L, Jougla E, Bevilacqua S, et al. Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy. Cancer 2004;101:317–24.[CrossRef][Web of Science][Medline]
3 Herida M, Mary-Krause M, Kaphan R, Cadranel J, Poizot-Martin I, Rabaud C, et al. Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients. J Clin Oncol 2003;21:3447–53.
4 Parker MS, Leveno DM, Campbell TJ, Worrell JA, Carozza SE. AIDS-related bronchogenic carcinoma: fact or fiction? Chest 1998;113:154–61.
5 Rankin JA, Collman R, Daniele RP. Acquired immune deficiency syndrome and the lung. Chest 1988;94:155–64.
6 Tirelli U, Spina M, Sandri S, Serraino D, Gobitti C, Fasan M, et al. Lung carcinoma in 36 patients with human immunodeficiency virus infection. The Italian Cooperative Group on AIDS and Tumors. Cancer 2000;88:563–9.[CrossRef][Web of Science][Medline]
7 Tammemagi CM, Neslund-Dudas C, Simoff M, Kvale P. Impact of comorbidity on lung cancer survival. Int J Cancer 2003;103:792–802.[CrossRef][Web of Science][Medline]
8 Vyzula R, Remick SC. Lung cancer in patients with HIV-infection. Lung Cancer 1996;15:325–39.[CrossRef][Medline]
9 Moses AV, Williams S, Heneveld ML, Strussenberg J, Rarick M, Loveless M, et al. Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors. Blood 1996;87:919–25.
10 Sparano JA, Lee S, Henry DF, Ambinder RF, Von Roenn J, Tirelli U, et al. Infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin's lymphoma: a review of the Einstein, Aviano, and ECOG experience in 182 patients. J Acquir Immune Defic Syndr 2000;23:A11, abstract S15.[CrossRef]
11 von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Duan SX, Fogelman SM, et al. Protease inhibitors as inhibitors of human cytochrome P450: high risk associated with ritonavir. J Clin Pharmacol 1998;38:106–11.[Abstract]
12 Yana T, Negoro S, Takada Y, Yokota S, Fukuoka M and West Japan Lung Cancer Group. Phase I study of amrubicin (SM-5887), a 9-amino-anthracycline, in previously untreated patients with extensive stage small-cell lung cancer (ES-SCLC). Proc Am Soc Clin Oncol 1998;17:450a.
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