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Complete Remission of Pulmonary Spindle Cell Carcinoma After Treatment With Oral Germanium Sesquioxide* FREE TO VIEW

Mark G. Mainwaring, MD, PhD; Christopher Poor, MD; Dani S. Zander, MD; Eloise Harman, MD, FCCP
Author and Funding Information

*From the Department of Medicine, Divisions of Hematology and Oncology (Dr. Mainwaring) and Pulmonary Medicine (Drs. Poor and Harman), and Department of Pathology, Immunology, and Laboratory Medicine (Dr. Zander), University of Florida College of Medicine and Veterans Affairs Medical Center, Gainesville, FL.

Correspondence to: Mark G. Mainwaring, MD, PhD, Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Box 100277, Gainesville, FL 32610; e-mail: mainwmg@medicine.ufl.edu



Chest. 2000;117(2):591-593. doi:10.1378/chest.117.2.591
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Published online

Spindle cell carcinoma (SCC) is a rare form of lung cancer representing 0.2 to 0.3% of all primary pulmonary malignancies. Even with combined surgery, chemotherapy, and radiation therapy, these tumors are associated with a poor prognosis and only 10% of patients survive 2 years after diagnosis. We describe a patient with an unresectable SCC who, following no response to conventional treatment with combined modality therapy, chose to medicate herself with daily doses of germanium obtained in a health food store. She noted prompt symptomatic improvement and remains clinically and radiographically free of disease 42 months after starting her alternative therapy.

Figures in this Article

The patient is a 47-year-old woman admitted with shortness of breath and cough. She had been in good health until 5 months earlier, when she noted mild dyspnea and a nonproductive cough. These symptoms progressed to include pleuritic chest pain and night sweats. Her medical history included childhood asthma. Physical examination revealed decreased breath sounds throughout the left lung field. Thoracic CT showed atelectasis of the left lung and a mass measuring 3.4 × 4.5 cm extending posterior to the left mainstem bronchus and displacing it anteriorly (Fig 1 , top, A). During bronchoscopy, an endobronchial lesion producing 75% occlusion of the left main bronchus was visualized. Biopsy specimens were obtained. At thoracotomy, the lung mass encircled the pulmonary artery and invaded the esophagus, the posterior wall of the pericardium, and the right pulmonary vein, and was deemed unresectable. Additional biopsy specimens were obtained.

Pathologic Findings

Bronchoscopic and open biopsies showed a proliferation of spindle-shaped cells with pleomorphic nuclei, variable amounts of cytoplasm with basophilia, and occasional mitoses (Fig 2 , top, A). Small foci of dysplastic squamous epithelium merged with the spindle cells (Fig 2, middle, B). Immunohistochemical stains for cytokeratin (MAK 6 and CAM 5.2) decorated the cytoplasm of occasional neoplastic cells (Fig 2, bottom, C) consistent with spindle cell carcinoma (SCC). Stains for leu M1, carcinoembryonic antigen, and B72.3 were negative. The background was myxoid with small amounts of collagen. The lesion eroded through the bronchial surfaces and was covered by a layer of fibrinous exudate.

Ultrastructural studies revealed abundant rough endoplasmic reticulum in the spindle-shaped tumor cells, and subplasmalemmal thin filaments with dense bodies in some of the neoplastic cells. Tonofilaments were not observed.

Follow-Up

The patient received chemotherapy including one cycle of etoposide/ifosfamide, and one cycle of paclitaxel/cisplatin followed by radiation therapy (4,500 cGy) to the thorax. Despite two additional cycles of mesna, adriamycin, ifosfamide, and dacarbazine, her symptoms worsened and she had radiographic evidence of tumor progression. The patient opted to discontinue all therapy.

While on a cruise 6 weeks later, the patient met a man who claimed that daily self-medication with germanium had cured him of oat cell carcinoma of the lung that was diagnosed 15 years earlier. The patient started daily self-medication with the same regimen (bis-betacarboxyethygermanium sesquioxide, 7.2 g qd, followed by a taper of the drug). Within a few days of beginning therapy, she felt her lungs “opening up” and required less supplemental oxygen. A chest radiograph 3 months later revealed 60% clearing of the left lung, and thoracic CT scans at 5 and 7 months showed near complete disappearance of the thoracic mass (Fig 1, bottom, B). At the time of this report, > 4 years after initial diagnosis, the patient continues to show no evidence of recurrent disease and has also continued to take low-dose germanium sesquioxide. The patient denies any significant side effects from her treatment.

Pulmonary SCC is a rare form of lung cancer that is more common in male than female patients (4 to 5:1), in smokers, and in patients between 50 and 80 years of age.1Carcinosarcoma, like SCC, contains malignant epithelial and sarcomatous elements, often forms a polypoid endobronchial mass, and may be part of a spectrum with SCC.2 Surgery remains the primary therapeutic modality, with the most important predictor of survival being the completeness of tumor resection.2In our patient, complete excision of the tumor was considered impossible because of the extension of the tumor into vital structures. Chemotherapy and radiation therapy were administered with the object of palliation, recognizing that a significant response was unlikely. Our patient’s lack of response to these agents is in accord with previous reports.3Overall survival is usually poor unless complete resection of the tumor can be accomplished.4

Germanium is an elemental metal discovered in 1886 and was used primarily in transistor technology. Preclinical studies during the 1970s showed that two germanium compounds had antineoplastic activity: spirogermanium and germanium sesquioxide. Preclinical studies with germanium compounds revealed antitumor activity in several tissue culture cell lines, including Walker 256 carcinosarcoma,5 and promoted several phase I/II clinical studies on advanced malignancies including lung,6breast,7 renal,8and prostate cancers.910 Unfortunately germanium sesquioxide and spirogermanium showed extremely limited activity in these studies and significant dose-related nephrotoxicity and neurotoxicity.11

Clinically and radiographically, our patient experienced complete tumor regression that was temporally related to the initiation of germanium therapy. While the precise mechanism underlying this patient’s response to germanium sesquioxide is not known, this compound has been reported to enhance immunity through stimulation of T cells, natural killer cells, lymphokines, and macrophage activity,12 and may have played a role in promoting tumor cell ablation in this patient. Less likely, although equally interesting, is the possibility that this patient had a “spontaneous remission” of a particularly aggressive malignancy unrelated to chemotherapy, radiation therapy, or germanium use. Although the promoting event that lead to the dramatic and durable improvement seen in this patient cannot be absolutely determined, the use of germanium sesquioxide may merit further studies in the treatment of unresectable SCC.

Abbreviation: SCC = spindle cell carcinoma

Figure Jump LinkFigure 1. Top, A: a CT of the thorax at the level of the aortic arch revealing a 3.5 × 4.5 × 6.5-cm left hilar mass. Bottom, B: a CT of the thorax after self-medication with germanium sesquioxide for 5 months, showing resolution of the hilar mass and left lung atelectasis.Grahic Jump Location
Figure Jump LinkFigure 2. Top, A: an endobronchial lesion associated with extensive ulceration of the bronchial surface. Small foci of dysplastic squamous epithelium merge with the predominant spindle cells (hematoxylin-eosin, original magnification × 100). Middle, B: spindle-shaped tumor cells with pleomorphic nuclei, variable amounts of basophilic cytoplasm, and occasional mitoses (arrow), in a myxoid background with a mixed inflammatory infiltrate consistent with SCC (hematoxylin-eosin, original magnification × 400). Bottom, C: occasional neoplastic cells (arrows) show cytoplasmic staining for cytokeratin consistent with SCC (immunoperoxidase stain with MAK 6 antibody, original magnification × 200).Grahic Jump Location
Dail, DH, Hammar, SP (1994)Pulmonary pathology 2nd ed. ,1310-1312 Springer-Verlag. New York, NY:
 
Nappi, O, Glasner, SD, Swanson, PE, et al Biphasic and monophasic sarcomatoid carcinomas of the lung: a reappraisal of “carcinosarcomas” and “spindle-cell carcinomas.”Am J Clin Pathol1994;102,331-340. [PubMed]
 
Grahmann, PR, Swoboda, L, Bonnet, R, et al Carcinosarcoma of the lung: three case reports and literature review.Thorac Cardiovasc Surg1993;41,312-317. [PubMed] [CrossRef]
 
Shyu, HL, Huang, BS, Cheng, CY, et al Carcinosarcoma of the lung: an analysis of 6 operated cases.Chung-Hua I Hseuh Tsa Chih1994;53,363-368
 
Kopf-Maier, P Complexes of metals other than platinum as antitumor agents.Eur J Clin Pharmacol1994;47,1-16. [PubMed]
 
Dhingra, HM, Umsawasdi, T, Chiuten, DF, et al Phase II study of spirogermanium in advanced (extensive) non-small cell lung cancer.Cancer Treat Rep1986;70,673-674. [PubMed]
 
Kuebler, JP, Tormey, DC, Harper, GR, et al Phase II study of spirogermanium in advanced breast cancer.Cancer Treat Rep1984;68,1515-1516. [PubMed]
 
Schulman, P, Davis, RB, Ralfa, S, et al Phase II trial of spirogermanium in advanced renal cell carcinoma: a Cancer and Leukemia Group B study.Cancer Treat Rep1984;68,1305-1306. [PubMed]
 
Dexeus, FH, Logothetis, C, Samuels, ML, et al Phase II study of spirogermanium in metastatic prostate cancer.Cancer Treat Rep1986;70,1129-1130. [PubMed]
 
Vogelzang, NJ, Gesme, DH, Kennedy, BJ A phase II study of spirogermanium in advanced human malignancy.Am J Clin Oncol1985;8,341-344. [PubMed]
 
Schauss, AG Nephrotoxicity and neurotoxicity in humans from organogermanium compounds and germanium dioxide.Biol Trace Elem Res1991;29,267-280. [PubMed]
 
Suzuki, F, Brutkiewicz, RR, Pollard, RB Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (GE-132).Anticancer Res1986;6,177-182. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Top, A: a CT of the thorax at the level of the aortic arch revealing a 3.5 × 4.5 × 6.5-cm left hilar mass. Bottom, B: a CT of the thorax after self-medication with germanium sesquioxide for 5 months, showing resolution of the hilar mass and left lung atelectasis.Grahic Jump Location
Figure Jump LinkFigure 2. Top, A: an endobronchial lesion associated with extensive ulceration of the bronchial surface. Small foci of dysplastic squamous epithelium merge with the predominant spindle cells (hematoxylin-eosin, original magnification × 100). Middle, B: spindle-shaped tumor cells with pleomorphic nuclei, variable amounts of basophilic cytoplasm, and occasional mitoses (arrow), in a myxoid background with a mixed inflammatory infiltrate consistent with SCC (hematoxylin-eosin, original magnification × 400). Bottom, C: occasional neoplastic cells (arrows) show cytoplasmic staining for cytokeratin consistent with SCC (immunoperoxidase stain with MAK 6 antibody, original magnification × 200).Grahic Jump Location

Tables

References

Dail, DH, Hammar, SP (1994)Pulmonary pathology 2nd ed. ,1310-1312 Springer-Verlag. New York, NY:
 
Nappi, O, Glasner, SD, Swanson, PE, et al Biphasic and monophasic sarcomatoid carcinomas of the lung: a reappraisal of “carcinosarcomas” and “spindle-cell carcinomas.”Am J Clin Pathol1994;102,331-340. [PubMed]
 
Grahmann, PR, Swoboda, L, Bonnet, R, et al Carcinosarcoma of the lung: three case reports and literature review.Thorac Cardiovasc Surg1993;41,312-317. [PubMed] [CrossRef]
 
Shyu, HL, Huang, BS, Cheng, CY, et al Carcinosarcoma of the lung: an analysis of 6 operated cases.Chung-Hua I Hseuh Tsa Chih1994;53,363-368
 
Kopf-Maier, P Complexes of metals other than platinum as antitumor agents.Eur J Clin Pharmacol1994;47,1-16. [PubMed]
 
Dhingra, HM, Umsawasdi, T, Chiuten, DF, et al Phase II study of spirogermanium in advanced (extensive) non-small cell lung cancer.Cancer Treat Rep1986;70,673-674. [PubMed]
 
Kuebler, JP, Tormey, DC, Harper, GR, et al Phase II study of spirogermanium in advanced breast cancer.Cancer Treat Rep1984;68,1515-1516. [PubMed]
 
Schulman, P, Davis, RB, Ralfa, S, et al Phase II trial of spirogermanium in advanced renal cell carcinoma: a Cancer and Leukemia Group B study.Cancer Treat Rep1984;68,1305-1306. [PubMed]
 
Dexeus, FH, Logothetis, C, Samuels, ML, et al Phase II study of spirogermanium in metastatic prostate cancer.Cancer Treat Rep1986;70,1129-1130. [PubMed]
 
Vogelzang, NJ, Gesme, DH, Kennedy, BJ A phase II study of spirogermanium in advanced human malignancy.Am J Clin Oncol1985;8,341-344. [PubMed]
 
Schauss, AG Nephrotoxicity and neurotoxicity in humans from organogermanium compounds and germanium dioxide.Biol Trace Elem Res1991;29,267-280. [PubMed]
 
Suzuki, F, Brutkiewicz, RR, Pollard, RB Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (GE-132).Anticancer Res1986;6,177-182. [PubMed]
 
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