PATRICK J. LOEHRER, SR., M.D.
Published Research
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1: Clin Lung Cancer. 2004 Jul;6(1):28-32.  
 
Thymoma and thymic carcinoma: therapeutic approaches.

Kurup A, Loehrer PJ Sr.

Department of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.

Thymomas and thymic carcinomas, which are rare epithelial tumors arising from the thymus gland, are the most common tumors of the anterior mediastinum. Thymomas are generally encapsulated, slow-growing tumors that have a "bland" histologic appearance. Thymic carcinomas possess more overtly malignant histologic features than thymomas and are more likely to present as invasive or disseminated disease. Surgery is the treatment of choice for localized thymic tumors, with complete resection being the most important prognostic factor. Complete resection also improves survival in locally invasive thymic tumors. Adjuvant postoperative radiation therapy may improve the outcome in patients with invasive disease, although the data are conflicting. Multimodal regimens, including neoadjuvant combination chemotherapy, surgery, and/or postoperative radiation therapy, are recommended for patients with advanced thymomas and thymic carcinomas. Use of octreotide plus prednisone has produced responses in thymomas, but the dosing and schedule have not been clearly defined. Prospective studies have been limited, and, as such, enrollment in clinical trials is encouraged.

2: Br J Cancer. 2004 Jun 1;90(11):2181-5.  
 
Absence of human T-cell lymphotropic virus type I and human foamy virus in thymoma.

Li H, Loehrer PJ Sr, Hisada M, Henley J, Whitby D, Engels EA.

Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, 6120 Executive Blvd., EPS 8010, Rockville, MD 20892, USA.

The cause of thymoma, a rare malignancy of thymic epithelial cells, is unknown. Recent studies have reported the detection of DNA from human T-cell lymphotropic virus type I (HTLV-I) and human foamy virus (HFV) in small numbers of thymoma tumours, suggesting an aetiologic role for these retroviruses. In the present study, we evaluated 21 US thymoma patients and 20 patients with other cancers for evidence of infection with these viruses. We used the polymerase chain reaction to attempt to amplify viral DNA from tumour tissues, using primers from the pol and tax (HTLV-I) and gag and bel1 (HFV) regions. In these experiments, we did not detect HTLV-I or HFV DNA sequences in any thymoma or control tissues, despite adequate sensitivity of our assays (one HTLV-I copy per 25 000 cells, one HFV copy per 7500 cells). Additionally, none of 14 thymoma patients evaluated serologically for HTLV I/II infection was positive by enzyme-linked immunoassay (ELISA), while five (36%) had indeterminate Western blot reactivity. In comparison, one of 20 US blood donors was HTLV-I/II ELISA positive, and nine (45%) donors, including the ELISA-positive donor, had indeterminate Western blot reactivity. Western blot patterns varied across individuals and consisted mostly of weak reactivity. In conclusion, we did not find evidence for the presence of HTLV-I or HFV in US thymoma patients.

3: J Cancer Res Clin Oncol. 2004 Apr;130(4):222-4. Epub 2004 Feb 5.  
 
Tyrosine kinase receptor expression in thymomas.

Henley JD, Cummings OW, Loehrer PJ Sr.

Department of Pathology, Indiana University School of Medicine, Clarian Health Partners, 550 North University Blvd, Rm 3465, Indianapolis 46202, USA. jhenley@iupui.edu

PURPOSE: Promising new therapies for neoplasia include tyrosine kinase receptor antagonists. Tyrosine kinase oncogenes present an appealing anti-tumor drug target since they play an integral role in a variety of cellular responses including cell proliferation and differentiation. We previously demonstrated a high rate of epidermal growth factor receptor (EGFR) expression in advanced-stage thymic epithelial tumors. More recently, we have examined c-KIT (CD117) expression in a similar series of tumors. METHODS: Tumor from 35 patients seen at our institution for treatment of advanced-stage thymoma was available. Twenty thymomas and 15 thymic carcinomas were assessed for c-KIT expression. Tissue sections of tumor were stained immunohistochemically with anti-c-KIT (Oncogene). Either cytoplasmic or membrane staining was considered positive. Appropriate controls were performed. Positive staining for c-KIT was present in 12 tumors (11 thymic carcinomas and 1 thymoma). RESULTS: In distinction to EGFR, c-KIT is expressed more commonly in thymic carcinomas (73% of carcinomas) than in thymoma (5% of thymomas). CONCLUSIONS: An EGFR negative/c-KIT positive staining pattern is typical of thymic carcinoma, whereas thymomas are generally EGFR positive/c-KIT negative. Possible therapeutic implications of these observations remain to be determined.

4: Semin Neurol. 2004 Mar;24(1):63-73.  
 
Thymoma: current medical and surgical management.

Kesler KA, Wright CD, Loehrer PJ Sr.

Thoracic Division, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

Thymoma is a rare neoplasm usually with an indolent growth pattern; however, local invasion and/or dissemination may occur. Surgery has been the standard of care for early stage disease with good to excellent cure rates anticipated. This neoplasm has been found to be relatively sensitive to cisplatinum-based chemotherapy as compared with most other epithelial tumors. Aggressive multimodality therapy therefore can result in long-term disease-free survival for patients presenting with locally advanced or even disseminated disease. This chapter outlines the current medical and surgical treatment options for thymoma.

5: J Clin Oncol. 2004 Jan 15;22(2):293-9.  
 
Erratum in:
Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial.

Loehrer PJ Sr, Wang W, Johnson DH, Aisner SC, Ettinger DS; Eastern Cooperative Oncology Group Phase II Trial.

Indiana University Medical Center, Indianapolis, IN 46202, USA. ploehrer@iupui.edu.

PURPOSE: To determine the objective response rate, duration of remission and toxicity of octreotide alone or with the later addition of prednisone in patients with unresectable, advanced thymic malignancies in whom the pretreatment octreotide scan was positive. PATIENTS AND METHODS: Forty-two patients with advanced thymoma or thymic carcinoma were entered onto the trial, of whom 38 were fully assessable (one patient had inconclusive histology; three patients had negative octreotide scan). Patients received octreotide 0.5 mg subcutaneously tid. At 2 months, patients were evaluated. Responding patients continued to receive octreotide alone; patients with progressive disease were removed from the study. All others received prednisone 0.6 mg/kg orally qid for a maximum of 1 year. RESULTS: Two complete (5.3%) and 10 partial responses (25%) were observed (four partial responses with octreotide alone; the remainder with octreotide plus prednisone). None of the six patients without pure thymoma responded. The 1- and 2-year survival rates were 86.6% and 75.7%, respectively. Patients with an Eastern Cooperative Oncology Group performance status of 0 lived significantly longer than did those with a performance status of 1 (P =.031). CONCLUSION: Octreotide alone has modest activity in patients with octreotide scan-positive thymoma. Prednisone improves the overall response rate but is associated with increased toxicity. Additional studies with the agent are warranted.
6: J Cancer Res Clin Oncol. 2002 Mar;128(3):167-70. Epub 2002 Jan 30.  
 
Epidermal growth factor receptor expression in invasive thymoma.

Henley JD, Koukoulis GK, Loehrer PJ Sr.

Department of Pathology, Indiana University School of Medicine, Clarian Health Partners, 550 North University Blvd., Rm 3465, Indianapolis, IN 46202, USA. jhenley@iupui.edu

PURPOSE: Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with intrinsic tyrosine kinase activity. Activation results in a variety of cellular responses including cell proliferation and differentiation. In clinical trials, anti-EGFR is showing promise in the treatment of solid tumors expressing EGFR. Thus, we assessed EGFR expression in a series of thymic epithelial tumors. METHODS: Tumors from 37 patients seen at Indiana University School of Medicine (IUMC) for treatment of thymoma (31 patients) or thymic carcinoma (six patients) were assessed for EGFR expression. Five-micron sections of formalin-fixed, paraffin-embedded tumor (28 invasive and/or metastatic thymomas, six thymic carcinomas, and three non-invasive thymomas) were stained with anti-EGFR. Any degree of cytoplasmic membrane staining of tumor cells was considered positive; furthermore, staining was scored 0 to 3+ using criteria as standardized for HER-2/neu assessment of breast carcinoma. Appropriate controls were performed. RESULTS: Positive staining of tumor was observed in 28 tumors (23 invasive and/or metastatic thymomas, two thymic carcinomas, and three non-invasive thymomas). CONCLUSIONS: EGFR is expressed in a high percentage of thymic epithelial tumors. EGFR is often strongly expressed and is a potential therapeutic target in patients with malignant thymic tumors. We are pursuing additional studies to assess anti-EGRF in the treatment of patients with advanced thymoma.

7: Bone Marrow Transplant. 2001 Sep;28(5):435-8.  
 
High-dose carboplatin with etoposide in patients with recurrent thymoma: the Indiana University experience.

Hanna N, Gharpure VS, Abonour R, Cornetta K, Loehrer PJ Sr.

Indiana University, Indianapolis, IN 46202, USA.

Thymoma is a chemotherapy-sensitive tumor with a 30-50% 5-year survival in previously untreated patients. Unfortunately, durable CRs with salvage chemotherapy are rarely observed. We initiated a phase II trial of high-dose carboplatin and etoposide in patients with relapsed thymoma or thymic carcinoma. All patients had progressive disease (PD) after initial or salvage chemotherapy, but were not cisplatin-refractory. PBSCs were mobilized using 10 microg/kg/day G-CSF. Patients received carboplatin 700 mg/m(2) and etoposide 750 mg/m(2) i.v. on days -5, -4, -3. Five patients were enrolled and evaluated after tandem transplants 4 weeks apart. All patients had pleural-based and lung parenchymal metastasis, one or two prior surgeries and two or more courses of prior cisplatin-based chemotherapy regimens. Chemotherapy was well tolerated, although grade IV hematological toxicity occurred in all patients. Progression-free survival following HDC ranged from 3.5 to 16.5 months. One patient maintained a CR for 12.8 months, then died from an unrelated cause. With a minimum of 2 years follow-up for all patients, three of five patients remain alive at 26+, 36+, and 49+ months. High-dose carboplatin and etoposide in relapsed thymoma is feasible with acceptable toxicity; however, these limited data do not appear superior to standard-dose salvage therapy.
8: Cancer. 2001 Jun 1;91(11):2010-5.  
 
Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial.

Loehrer PJ Sr, Jiroutek M, Aisner S, Aisner J, Green M, Thomas CR Jr, Livingston R, Johnson DH.

Department of Medicine, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, Indiana, USA. ploehrer@iupui.edu

BACKGROUND: Patients with thymic tumors (thymoma and thymic carcinoma) are known to respond to a variety of chemotherapeutic agents, including single-agent ifosfamide and cisplatin with etoposide. The purpose of this trial was to evaluate the response rate, progression free survival, overall survival, and toxicity of combined etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced thymoma and thymic carcinoma. METHODS: From July 1995 through February 1997, 34 patients with advanced thymoma or thymic carcinoma were entered on trial to receive etoposide (75 mg/m2 on Days 1-4) ifosfamide (1.2 g/m2 on Days 1-4), and cisplatin (20 mg/m2 on Days 1-4). Cycles were repeated every 3 weeks for four total cycles. RESULTS: Among 28 evaluable patients (pathology review excluded 6 patients), there were no complete responses and 9 partial responses (complete and partial responses combined, 32%; 95% confidence interval, 16-52%). The median follow-up was 43 months (range, 12.8-52.3 months), the median duration of response was 11.9 months (range, < 1-26 months), and the median overall survival was 31.6 months. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 89% and 70%, respectively. The toxicity was predominantly myelosuppression. CONCLUSIONS: The VIP regimen has moderate activity in patients with advanced thymic malignancies. However, with limited follow-up, the results of this trial appear to be inferior to other chemotherapy regimens reported in large Phase II trials performed in patients with this disease. Copyright 2001 American Cancer Society.
9: Cancer Treat Res. 2001;105:277-302.  

Thymic malignancies.

Loehrer PJ Sr, Wick MR.

Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Thymomas and thymic carcinomas are unique tumors of the anterior mediastinum. The association of a variety of different paraneoplastic syndromes with such lesions has fascinated physicians and researchers for years. Most recently, it has been demonstrated by numerous authors that thymomas are chemosensitive tumors. Their indolent nature and relative rarity have made evaluation through prospective randomized clinical trials extremely difficult. Further information regarding the molecular nature of these neoplasms and immunologic aspects is needed in future investigation.

10: Ann Med. 1999 Oct;31 Suppl 2:73-9.  

Current approaches to the treatment of thymoma.

Loehrer PJ Sr.

Indiana University Medical Center, The Walther Cancer Institute, Indianapolis 46202-5289, USA. ploehrer@iupui.edu

Thymoma is an unusual tumour, but it is the most common malignancy in the anterior mediastinum. This tumour is unique in its frequent association with paraneoplastic syndrome and its potential for indolent growth. The distinction between thymomas and other tumours which arise in the anterior or superior mediastinum is important, and the optimal therapy for these malignancies is quite different. Indeed, even in advanced disease, systemic therapy may not only prolong the disease-free survival, but may also be curative in various malignancies. The therapy for patients with thymoma has been evolving over the past few years.

11: J Clin Oncol. 1999 Jul;17(7):2280-9.  
 
Thymoma: state of the art.

Thomas CR, Wright CD, Loehrer PJ.

Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. thomas@radonc.musc.edu

Thymoma is the most common tumor of the anterior mediastinum. This tumor is associated with unique paraneoplastic syndromes, such as myasthenia gravis, hypogammaglobulinemia, and pure red cell aplasia. The rarity of this tumor, however, has somewhat obscured the optimal treatment for this disease. For the majority of patients who present with localized tumor, surgical extirpation remains the standard of choice. Adjuvant radiotherapy seems to improve local control and survival. In more advanced disease, systemic therapy has been demonstrated to produce a 50% to 80% objective response rate. These observations have led to the development of multimodality therapy for the treatment of patients with advanced thymoma. In this article, we will review the current perspectives on the management of early stage and advanced thymoma.

12: Am J Clin Oncol. 1998 Apr;21(2):180-4.  
 
Paclitaxel plus gallium nitrate and filgrastim in patients with refractory malignancies: a phase I trial.

Sandler A, Fox S, Meyers T, Christou A, Weber G, Gonin R, Loehrer PJ, Einhorn LH, Dreicer R.

Division of Hematology/Oncology, Indiana University, Indianapolis, USA.

To determine the maximally tolerated dose of paclitaxel with and without filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a 120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m2/24 hours, 40 patients were entered onto a trial lasting from September 1994 to September 1996. Eligibility included a diagnosis of an advanced malignancy not amenable to curative therapy and up to one previous chemotherapy regimen for metastatic disease. Gallium was administered at a fixed dose of 300 mg/m2/day as a continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m2 was given concurrently with the last 24 hours of the gallium as a 24-hour intravenous infusion. Cycles were repeated every 21 days. Once the maximum tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 microg/kg/day days 7-16) was added and paclitaxel dose escalation continued. The MTD for paclitaxel without G-CSF was 110 mg/m2 and 225 mg/m2 with G-CSF, with neutropenia being the dose-limiting toxicity. A partial response was noted in a patient who had thymoma and a complete response was achieved in a patient who had colon cancer. The recommended phase II dosage is gallium nitrate at 300 mg/m2/day over 120 hours, with paclitaxel at 110 mg/m2 over 24 hours without G-CSF or 225 mg/m2 over 24 hours with G-CSF and 0.5 mg calcitriol on days 1 through 7. Further trials of this modified regimen for outpatient administration are in progress.
13: J Clin Oncol. 1997 Sep;15(9):3093-9.  
 
Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an intergroup trial.

Loehrer PJ Sr, Chen M, Kim K, Aisner SC, Einhorn LH, Livingston R, Johnson D.

Department of Medicine, Indiana University Medical Center, Indianapolis 46202-5265, USA.

PURPOSE: To determine the response rate of cisplatin plus doxorubicin plus cyclophosphamide (PAC) in patients with limited-stage unresectable thymoma. In addition, this study was undertaken to determine the toxicity, progression-free survival, and overall survival of combined-modality therapy with PAC plus radiation therapy. PATIENTS AND METHODS: Patients with a histologic diagnosis of limited-stage unresectable thymoma or thymic carcinoma were eligible. Further requirements included a Karnofsky Performance Score of > 60, no prior radiation to the chest, and adequate bone marrow, hepatic, and renal function. No patient had undergone chemotherapy previously. Patients received two to four cycles (repeated every 3 weeks) of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) followed by a total dosage of 54 Gy to the primary tumor and regional lymph nodes for patients with a stable, partial, or complete response to chemotherapy. RESULTS: From November 1983 through January 1995, 26 patients were entered onto the trial. Three patients were ineligible on the basis of pathologic review (lung cancer, germ cell cancer, lymphoma). Toxicity, primarily hematologic, was mild, with only one early death due to a perforated abdominal viscus. Among the 23 assessable patients, there were five complete and 11 partial responses to chemotherapy (overall response rate, 69.6%). The median time to treatment failure was 93.2 months (range, 3 to 99.2+ months), and the median survival time was 93 months (range, 1 to 110 months). The 5-year survival rate is 52.5%. CONCLUSIONS: PAC combination chemotherapy produces response rates in the management of patients with limited thymoma. Combined-modality therapy is feasible and associated with prolonged progressive-free survival. The benefit of combined-modality therapy over radiation therapy alone is suggested for patients with unresectable thymoma.

14: Curr Opin Oncol. 1996 Mar;8(2):112-9.  

Thymic neoplasms.

Debono DJ, Loehrer PJ.

Indiana University Medical Center, Division of Hematology/Oncology, University Hospital, Indianapolis 42620-5265, USA.

Thymic carcinomas and thymomas are neoplasms of the epithelial cells of the thymus. Extensive study of the histopathology of these tumors has provided insight into the clinical behavior of various pathological subtypes. Establishment of a uniform staging system has facilitated the prospective study of thymic tumors, and it has helped to provide the necessary framework for international cooperation in the study of these diseases. This review explains the pathological nomenclature used in the classification of these tumors, examines the prospective clinical trials that have been completed to date, and discusses the interesting paraneoplastic phenomena associated with thymomas.

15: J Immunother Emphasis Tumor Immunol. 1995 Oct;18(3):179-84.  

A phase II trial of subcutaneously administered recombinant human interleukin-2 in patients with relapsed/refractory thymoma.

Gordon MS, Battiato LA, Gonin R, Harrison-Mann BC, Loehrer PJ Sr.

Clinical Hematology and Cytokine Program, Indiana University School of Medicine, Indianapolis, USA.

The thymus is the site of T-cell maturation and contains T-cell precursors that differentiate into cytolytic T lymphocytes (CTLs) in vitro in the presence of interleukin-2 (IL-2). Malignant thymoma is often associated with a lymphocytic infiltration of these precursors. The antitumor effects of IL-2 are mediated in part by activated CTLs. Based on these considerations and anecdotal reports of its anti-tumor activity in thymoma, we conducted a Phase II trial of IL-2 in 14 patients with thymoma. IL-2 was administered s.c. at a dose of 12 x 10(6) IU/m2/day for 5 days for 4 weeks followed by a 2-week rest period. Patients were evaluated for response after each 6-week cycle, and those tolerating therapy with no disease progression were eligible for a maximum of 4 cycles. All patients had failed prior standard chemotherapy and 12 had received prior radiotherapy. All 14 patients were evaluable for toxicity and response. The median number of cycles received was two. One patient was removed from study during cycle 1 because of severe bronchospasm. Five patients required dose reductions for grade 3 toxicity (anorexia, nausea, hyperbilirubinemia, elevated SGPT, and skin desquamation, one patient each). Two patients developed new symptoms of myasthenia gravis while in the study and were removed (one for progressive disease, one for steroid requirement). There were no objective responses. The one patient who required steroids for newly diagnosed myasthenia gravis had a minor response. We conclude that subcutaneously administered IL-2, although it has acceptable toxicity, has no significant clinical activity in previously treated patients with advanced thymoma.

16: J Clin Oncol. 1994 Jun;12(6):1164-8.  
 
Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group.

Loehrer PJ Sr, Kim K, Aisner SC, Livingston R, Einhorn LH, Johnson D, Blum R.

Department of Medicine, Indiana University Medical Center, Indianapolis 46202.

PURPOSE: The purpose of this study was to evaluate the impact of cisplatin, doxorubicin, and cyclophosphamide (PAC) in patients with advanced thymoma with respect to response rate, duration of remission, and overall survival. PATIENTS AND METHODS: Assessable patients with thymoma (n = 29) or thymic carcinoma (n = 1) with metastatic or locally progressive recurrent disease following radiotherapy were treated with intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) with normal saline hydration. Courses were repeated every 3 weeks for a maximum of eight cycles of therapy. RESULTS: Toxicity, which was primarily hematologic, was mild, with only one patient developing a fever associated with neutropenia. Three complete responses (CRs) and 12 partial responses (PRs) were observed (CR+PR rate, 50%; 95% confidence interval, 31.3% to 68.7%). Ten patients had stable disease. The median duration of response was 11.8 months (range, 0.9 to 70.5+), the time to treatment failure 18.4 months (range, 0.8 to 91.9+), and median survival time 37.7 months (range, 2 to 91.9+). CONCLUSION: This trial demonstrates that objective response rates and prolonged survival can be achieved in patients with advanced thymoma.

17: Drugs. 1993 Apr;45(4):477-87.  

Thymomas. Current experience and future directions in therapy.

Loehrer PJ.

Department of Medicine, Indiana University Medical Center, Indianapolis.

18: Cancer. 1993 Feb 15;71(4):1219-23.  

Thymic carcinoma. A distinct clinical entity responsive to chemotherapy.

Weide LG, Ulbright TM, Loehrer PJ Sr, Williams SD.

Department of Medicine, Indiana University, Indianapolis.

BACKGROUND. Thymic carcinomas are rare tumors of the anterior mediastinum. These tumors are distinct thymic neoplasms that differ from their more common counterpart, thymoma. As opposed to thymomas, thymic carcinomas are histologically malignant neoplasms with a clinical course that tends to be much more aggressive than that of patients with thymoma. METHODS. Between 1984 and 1990, five patients with thymic carcinoma treated with cisplatin-based combination chemotherapy were seen at Indiana University Hospital. These patients' diagnoses, courses, and treatments were reviewed. RESULTS. Three patients responded (two completely) to cisplatin-based chemotherapy. CONCLUSIONS. This form of chemotherapy merits additional study in such patients, and our experience indicates that at least some will have clinically meaningful responses. The optimum regimen is unclear, but would contain cisplatin and probably should be similar to that used in germ cell tumors.

19: Ann Intern Med. 1990 Oct 1;113(7):520-4.  

Chemotherapy for advanced thymoma. Preliminary results of an intergroup study.

Loehrer PJ Sr, Perez CA, Roth LM, Greco A, Livingston RB, Einhorn LH.

Indiana University Hospital, Indianapolis.

OBJECTIVE: To determine the efficacy of combination therapy with cisplatin, doxorubicin, and cyclophosphamide alone or with radiotherapy for patients with extensive and those with limited unresectable thymoma. DESIGN: Nonrandomized, prospective phase I-II trial. SETTING: A Cooperative Oncology Group trial involving tertiary medical centers. PATIENTS: Twenty of twenty-two patients with measurable, extensive or limited, unresectable thymoma were evaluable for response. INTERVENTION: Patients were given cisplatin, 50 mg/m2 body surface area, doxorubicin, 50 mg/m2, and cyclophosphamide, 500 mg/m2, on day 1, with cycles repeated every 21 days until progression or until the maximally tolerated total doxorubicin dosage (for example, 450 mg/m2) was reached. Intravenous hydration with normal saline was administered during treatment courses. For responding patients with limited disease, 4500 cGy was administered to primary tumors after the second cycle of chemotherapy and before the initiation of the third cycle. MEASUREMENTS AND MAIN RESULTS: Three complete and eleven partial remissions were seen in 20 evaluable patients, for a total response rate of 70% (95% CI, 46% to 88%). The median duration of remission was 13 months with three patients remaining continuously disease free for over 2 years. The median survival time of all eligible patients was 59 months (CI, 22 months to infinity). Four patients developed infections, including listerial and aseptic meningitides, mucocutaneous candidiasis, and cryptococcal pneumonia, that were indicative of a defect in cell-mediated immunity. CONCLUSIONS: Combination therapy with cisplatin, doxorubicin, and cyclophosphamide frequently produces objective remissions in patients with advanced thymoma. Further experience with this treatment regimen is warranted to clarify potential prognostic factors in patients with unresectable thymoma.

20: Chest. 1985 Mar;87(3):377-80.  

Remission of invasive thymoma due to chemotherapy. Two patients treated with cyclophosphamide, doxorubicin, and vincristine.

Loehrer PJ, Bonomi P, Goldman S, Reddy S, Faber LP, Jensik R, Dainauskas JR.

Information regarding the effectiveness of chemotherapy in cases of invasive thymoma is limited. Two patients in whom the combination of cyclophosphamide, doxorubicin, and vincristine produced remission of invasive thymoma are described. The durations of remission were eight and seven months, respectively. In both patients, recurrence was observed at the site of bulky disease, and a secondary complete response continuing for 37 months was achieved in one of them with radiation therapy.