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Gemcitabine in Patients With Relapsed or Cisplatin-Refractory Testicular Cancer

From the Department of Hematology/Oncology, Internal Medicine II, Eberhard Karls University, Tübingen; Department of Internal Medicine, Klinikum Grosshadern, Munich; Department of Hematology/Oncology, Hannover Medical School, Hannover; Westdeutsches Tumorzentrum, University of Essen, Essen; Department of Internal Medicine, Städtisches Klinikum Leverkusen, Leverkusen; Department of Internal Medicine, Virchowklinikum, Free University of Berlin, Berlin; Department of Hematology/Oncology, University of Rostock, Rostock; and Department of Hematology/Oncology, University of Halle-Wittenberg, Halle, Germany.

Address reprint requests to C. Bokemeyer, MD, Department of Hematology/Oncology, Internal Medicine II, Eberhard Karls University, Otfried-Müller Str. 10, 72076 Tübingen, Germany; email carsten.bokemeyer{at}med.uni-tuebingen.de

	ABSTRACT

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PURPOSE: Despite generally high cure rates in patients with metastatic testicular germ cell tumors, patients with incomplete response to cisplatin-based first-line therapy or with relapsed disease after high-dose salvage chemotherapy have a very poor prognosis. This phase II study evaluates the use of gemcitabine in patients with intensively pretreated or cisplatin-refractory testicular germ cell cancers.

PATIENTS AND METHODS: Thirty-five patients (median age, 33 years) were enrolled; 31 patients were fully assessable. All patients had metastatic nonseminomatous germ cell tumors; eight patients had extragonadal primary tumors. Twenty patients (63%) had lung metastases, and 12 patients (39%) had liver metastases. The median number of prior cisplatin-based chemotherapy cycles was seven; 22 patients (71%) had received high-dose chemotherapy with autologous stem-cell transplantation, and 19 patients (61%) had received treatment with paclitaxel. Seventeen patients (54%) were considered refractory or absolutely refractory to chemotherapy.

RESULTS: Six of 31 assessable patients (19%) responded favorably to gemcitabine, 11 patients (35%) displayed no change, and 14 patients (45%) had disease progression. The median time to treatment failure was 4 months (range, 2 to 9+ months), and the median survival was 6 months (range, 2 to 23 months). Patients received a median of six gemcitabine applications. Ten patients (32%) required dose reductions, mainly owing to hematologic toxicity. Grade 3/4 granulocytopenia occurred in four patients (13%) and grade 3/4 thrombocytopenia in seven patients (22%). One case of severe sepsis was observed.

CONCLUSION: Gemcitabine displays antitumor activity in intensively pretreated and refractory germ cell tumors. Responses were observed in approximately 20% of patients, including three of 22 patients after previous high-dose chemotherapy and one of four patients with mediastinal tumors. Gemcitabine may be a reasonable palliative option for intensively pretreated patients and should be further investigated to define its role in the risk-adapted treatment strategies for germ cell tumors.

	INTRODUCTION

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THROUGH THE USE OF cisplatin-based combination chemotherapy, such as cisplatin, etoposide, and bleomycin, metastatic testicular germ cell cancer has become a model for a curable disease.^1,2 Cure is achieved in approximately 70% to 80% of patients. Patients relapsing after first-line chemotherapy are usually treated with carboplatin/etoposide–based high-dose chemotherapy plus autologous stem-cell rescue.^3,4 However, only 20% to 50% of these patients will achieve long-term survival. Patients relapsing again after high-dose therapy or those with disease refractory to platinum-based combination treatment have an extremely poor prognosis.^5,6 For these patients, the identification of new agents with significant antitumor activity in germ cell cancer remains a priority. However, several phase II studies investigating agents such as topotecan, vinorelbine, and high-dose epirubicin have failed to demonstrate effectiveness in relapsed germ-cell tumors.^7-9 Paclitaxel is one of the few drugs consistently reported to demonstrate activity in platinum-resistant testicular cancer in phase II studies.^10-12 Some centers have developed treatment strategies using paclitaxel as part of the combination treatment for patients with first relapse, combining it with cisplatin and/or ifosfamide.^13-16 The German Testicular Cancer Study Group investigated the paclitaxel, ifosfamide, and cisplatin regimen, given for three cycles as induction treatment before high-dose salvage therapy.¹⁷ With a substantial number of patients now also pretreated with paclitaxel, the search for new and effective palliative treatment in relapsed patients continues.

Owing to the observation of a significant response to gemcitabine in a female patient with cisplatin- and paclitaxel-refractory ovarian germ cell cancer,¹⁸ the German Testicular Cancer Study Group has started a formal phase II study evaluating the potential role of gemcitabine in relapsed and/or cisplatin-refractory testicular cancer. Gemcitabine is a new nucleoside analog (2'-difluorodeoxycytidine) with a number of unique cytotoxic properties. Its mechanism of action depends on phosphorylation and inhibition of the production of deoxynucleotide triphosphates required for normal DNA synthesis.¹⁹ This report describes the results of a phase II study of gemcitabine, given at a dose of 1,000 mg/m² intravenously over 30 minutes once weekly for 3 consecutive weeks, in intensively pretreated patients with testicular or extragonadal germ cell tumors.

	PATIENTS AND METHODS

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This phase II trial was approved by the Tübingen University Ethics Committee. All patients gave their informed consent. Eligibility criteria included the presence of progressive germ cell cancer and bidimensionally measurable disease, Karnofsky performance status above 60%, white blood cell count more than 2,500/µL, platelets more than 80,000/µL, adequate renal function (glomerular filtration rate > 60 mL/min and serum creatinine level < 1.5 times the upper normal value). Patients with relapsed disease after a minimum of two previous cisplatin-based chemotherapies or with tumor progression after high-dose chemotherapy plus autologous stem-cell rescue or patients with tumor progression during cisplatin-based first-line or salvage chemotherapy were eligible. Exclusion criteria were pretreatment with gemcitabine or concurrent treatment with other cytotoxic chemotherapy or radiotherapy of the indicator lesions, the presence of an active infection, symptomatic cardiovascular or cerebrovascular disease, or inadequate liver function (bilirubin > three times the upper normal value).

The pretreatment evaluations included history and physical examination with the documentation of measurable disease and performance status; serum tumor marker levels (alpha-fetoprotein [AFP], beta–human chorionic gonadotropin, and lactate dehydrogenase); liver function tests and creatinine levels; complete blood count with differential; and ECG, chest radiograph, and/or computed tomographic scans of all accessible tumor sites.

Treatment
Gemcitabine (Eli Lilly GmbH, Bad Homburg, Germany) was supplied as a lyophilized powder in sterile vials containing 200 or 1,000 mg of gemcitabine hydrochloride salt. Gemcitabine was given at a dose of 1,000 mg/m² as an intravenous infusion over 30 minutes once weekly for 3 consecutive weeks (days 1, 8, and 15), followed by a 1-week rest period. Patients received routine antiemetic treatment, usually with 5-hydroxytryptamine-3 antagonists, with one dose given before gemcitabine administration and a second dose given orally on the day of administration. For patients experiencing a flu-like syndrome after the gemcitabine application, the next administrations were preceded by oral dexamethasone (4 mg before, the evening after, and the next morning after gemcitabine application). A dose reduction to 50% was planned in the case of any grade 3 nonhematologic toxicity, and a cessation of therapy was planned in the case of grade 4 nonhematologic toxicity. For hematologic toxicity, a 50% dose reduction of gemcitabine was planned in the case of thrombocytopenia (50,000 to 74,000/µL) or neutrophil counts between 500 and 1,000/µL. No gemcitabine was given with neutrophil counts below 500/µL or thrombocyte counts below 50,000/µL until recovery of the blood counts. If no recovery was observed after 2 weeks, the patient was taken off-study. No routine use of hematopoietic growth factor was planned, but granulocyte colony-stimulating factor (G-CSF) could be given on an individual basis in instances of severe neutropenia. Treatment was routinely given on an outpatient basis.

Response Assessment and Treatment Duration
No other chemotherapy, hormonal therapy, or experimental medication was permitted while patients were on-study. Response and toxicity were graded according to World Health Organization (WHO) criteria. In addition, reduction in the size of a tumor and normalization of previously elevated tumor markers were considered a partial remission with marker normalization. Serum tumor markers were determined every 3 weeks. A greater than 75% reduction of previously elevated serum tumor markers during gemcitabine treatment was also considered a favorable response. In these cases, surgical resection of all residual masses was attempted if technically feasible. Only patients receiving at least three doses of gemcitabine were considered assessable for response. For patients with tumor response or at least disease stabilization, gemcitabine was continued until progression or until the occurrence of severe side effects. At least six weekly applications of gemcitabine were planned after achievement of the best response. Patients with severe nonhematologic toxicity ( WHO grade 3) or tumor progression were taken off-study.

	RESULTS

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Response
Overall, 35 patients with metastatic nonseminomatous germ cell tumors were enrolled. Four patients were excluded from further analysis: two were registered but never treated on-study, and two other patients received only one dose of gemcitabine and were then lost to follow-up. Thus, 31 patients with a median age of 33 years (range, 18 to 47 years), enrolled during the period from June 1996 to April 1998, were assessable. The patients' characteristics are listed in Table 1. Eight patients (26%) had extragonadal primary tumors, including four patients (13%) with primary mediastinal germ cell cancer. Metastatic sites predominantly included the lymphatic nodes and the lungs. However, almost 40% of patients had liver involvement, and 13% had brain metastases. Seventeen patients (55%) had two separate sites of disease involvement, and five patients (16%) had three or more different sites. All patients were intensively pretreated with cisplatin-based chemotherapy (median, seven cycles). Twenty-two patients (71%) had received previous high-dose chemotherapy regimens with autologous stem-cell transplantation. Nineteen patients (61%) had been previously treated with paclitaxel single-agent or combination chemotherapy. According to Indiana University criteria, six patients had never responded to prior therapy and were considered absolutely refractory to chemotherapy and 11 patients, who had relapsed within 4 weeks of treatment, were considered refractory.

Overall, six patients (19%) responded favorably to treatment with gemcitabine, including two patients who experienced a marker normalization as well as partial remission of lung and lymph node metastases in one patient and of lymph node and brain metastases in the other. This was surprising, because the latter patient had previously received irradiation for his brain metastases. Four patients had a more than 75% decline of elevated serum tumor markers (patient no. 1, decrease in AFP from 200,000 to 2,000 ng/mL; patient no. 2, decrease in beta–human chorionic gonadotropin from 4,500 to 300 IU/L; patient no. 3, decrease in lactate dehydrogenase from 2,500 to 180 U/L; patient no. 4, decrease in AFP from 800 to 40 ng/mL). Eleven patients (35%) had temporary disease stabilization (mean duration, 3 months; range, 2 to 9+ months), and 14 patients (45%) had disease progression despite gemcitabine treatment. The median time to gemcitabine failure for patients with favorable response or no change was 4 months (range, 2 to 9+ months); the median overall survival for all patients was 6 months (range, 2 to 23 months). Among the patients responding to gemcitabine treatment, three of 22 patients (14%) had relapsed after high-dose chemotherapy. Among the other subsets of patients, one of four patients with a late relapse of germ cell cancer as well as one of four patients with a primary mediastinal germ cell tumor also responded to gemcitabine. None of the patients with absolutely platinum-refractory disease responded, whereas three of 11 (27%) with refractory disease obtained a response to gemcitabine therapy (Table 2).

Toxicity
A total of 231 gemcitabine applications were given, with a median of six (range, three to 24) per patient. Dose reductions were necessary in approximately one third of patients. Toxicity is summarized in Table 3. Overall, nonhematologic toxicities were mild, and fever and nausea/vomiting were the main side effects. Each of these two side effects reached WHO grade 3 toxicity in only one patient.

In patients with intensive prior treatment and relapse after high-dose chemotherapy with stem-cell transplantation, hematologic toxicity was more pronounced, affecting 13% of patients with grade 3/4 granulocytopenia and 22% of patients with grade 3/4 thrombocytopenia. One patient developed a severe septic episode and required 2 weeks of hospitalization and antibiotic treatment. In six patients, the schedule for application of gemcitabine was changed from treatment on days 1, 8, and 15 to treatment on days 1 and 8, followed by 1 week off treatment, and then recycling on day 21. Only one patient experienced a severe septic episode after gemcitabine-induced granulocytopenia. The decision whether to use G-CSF was left to the discretion of the individual treating physician. Thirteen patients (44%) received intermittent support with G-CSF. There was no treatment-associated death.

	DISCUSSION

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The antitumor activity and toxicity of gemcitabine have been studied in patients with various solid tumors. A dose of 1,000 to 1,250 mg/m² of gemcitabine as a 30-minute infusion once weekly for 3 consecutive weeks has been the most widely used schedule. Significant improvement of tumor-related symptoms after gemcitabine administration has been reported in patients with advanced pancreatic cancer.²⁰ Antitumor activity has also been observed in bladder cancer, advanced breast cancer, ovarian cancer, and non–small-cell lung cancer.^21-24 In animal tumor models, gemcitabine shows activity across a range of tumors including breast cancer, ovarian cancer, lymphoma, myeloma, melanoma, and leukemia.¹⁹ The drug is well tolerated, with mild to intermediate flu-like symptoms or peripheral edemas being reported in 15% to 20% of patients. Leukopenia and thrombocytopenia of WHO grade 3/4 have been reported in 4% to 20% of patients. Minor skin toxicity with rash occurs in 5% to 10% of patients, whereas alopecia is rare.^19,22

This report summarizes the results of a phase II study of gemcitabine in 31 patients with relapsed and/or cisplatin-refractory germ cell cancer. Within this extensively pretreated patient population, more than two thirds had been treated with previous high-dose chemotherapy and autologous stem-cell transplantation and/or had received prior paclitaxel treatment owing to resistant disease. In addition, more than 50% were considered cisplatin refractory. Six patients showed a response to weekly applications of gemcitabine. This includes two patients with radiologic and marker remissions and four additional patients with a significant marker decline during treatment. Although the median duration of treatment with gemcitabine was short (4 months), the patients with the longest treatment duration received up to 24 applications of gemcitabine, resulting in a treatment period of 8 months.

Overall, toxicity of gemcitabine was mild, especially with respect to nonhematologic toxicities. Hematologic toxicity was more pronounced, most often resulting in thrombocytopenia. No severe bleeding episodes were observed; however, some patients intermittently received platelet transfusions. For six patients who had relapsed after high-dose salvage chemotherapy with autologous stem-cell transplantation, the schedule of weekly gemcitabine applications was shortened by 1 week (days 1 and 8 only) owing to hematologic toxicity. However, recycling was attempted on day 21 instead of day 28 in these patients.

A recent abstract reported the results of a phase II trial of gemcitabine in 21 multiply relapsed and platin-refractory testicular cancer patients. Investigators at Indiana University used a schedule of 1,200 mg/m² of gemcitabine on days 1, 8, and 15, repeated on day 28.²⁵ The treatment was well tolerated, and dose reductions were necessary in only three patients. However, fewer patients who had received previous high-dose chemotherapy were included. Three (20%) of 15 assessable patients responded to gemcitabine, one with a disappearance of liver metastases and marker normalization (complete response) and two with a significant (> 75%) reduction of serum tumor markers. Both that study and ours indicate the activity of gemcitabine in platin-refractory germ cell cancers, as did our previous case report of a female patient with platinum-resistant ovarian germ cell cancer.¹⁸

Gemcitabine has a novel and unique mechanism of action. Once inside the cell, it is progressively phosphorylated, and gemcitabine diphosphate acts as an inhibitor of ribonucleotide reductase, an enzyme responsible for catalyzing the production of deoxynucleotide triphosphates for DNA synthesis. Gemcitabine triphosphate competes with deoxycytidine triphosphate for incorporation into DNA. Once incorporated into DNA, only one more nucleotide is able to pair before the DNA chain is terminated. Thus, the error in the DNA chain is masked and may be less easily excised by proofreading exonuclease enzymes.^19,20,23 In addition, several mechanisms by which the gemcitabine activity is self-potentiated have been described. Thus, the specific mechanism of action of gemcitabine is largely different from those of other established cytotoxic drugs used in the treatment of testicular cancer.²⁶ Depending on the schedule used, the combination of gemcitabine with cisplatin has been reported to be synergistic in a number of in vitro and in vivo systems. Clinically, the combination of cisplatin and gemcitabine has been studied in patients with pancreatic cancer and is currently being evaluated in both bladder cancer and non–small-cell lung cancer.^19-21,23

In summary, this report indicates activity of gemcitabine in intensively pretreated testicular germ cell cancer patients. Further evaluation might include the investigation of its possible synergism with cisplatin at earlier stages of the disease or examination of the combination of gemcitabine with paclitaxel in refractory patients. The finding of gemcitabine as another active agent in conjunction with paclitaxel may also renew interest in testing the concept of alternating chemotherapy in the treatment of testicular cancer. Currently, gemcitabine appears to be a well-tolerated alternative that may be used instead of or after oral etoposide for palliative treatment in intensively pretreated germ cell cancer patients.

	ACKNOWLEDGMENTS

 
Supported in part by Eli Lilly GmbH, Bad Homburg, Germany.

We would like to thank E. Bock and G. Pflugrad-Jauch, Department of Hematology/Oncology, University of Tübingen, for their help in conducting, analyzing, and publishing this study. We also thank PD Dr. M. Arning of Eli Lilly GmbH, Germany, for scientific support.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
1. Bosl GJ, Motzer RJ: Testicular germ cell cancer. N Engl J Med 337:242-253, 1997[Free Full Text]

2. Einhorn LH: Treatment of testicular cancer: A new and improved model. J Clin Oncol 8:1777-1781, 1990[Abstract]

3. Nichols CR, Tricot G, Williams S, et al: Dose-intensive chemotherapy in refractory germ cell cancer: A phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation. J Clin Oncol 7:932-939, 1989[Abstract]

4. Siegert W, Beyer J, Strohscheer I, et al: High-dose treatment with carboplatin, etoposide and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: A phase I/II study. J Clin Oncol 12:1223-1231, 1994[Abstract/Free Full Text]

5. Nichols CR, Roth BJ, Loehrer PJ, et al: Salvage chemotherapy for recurrent germ cell cancer. Semin Oncol 5:102-108, 1994 (suppl 12)

6. Motzer RJ, Mazumdar M, Bosl GJ, et al: High-dose carboplatin, etoposide, and cyclophosphamide for patients with refractory germ cell tumors: Treatment results and prognostic factors for survival and toxicity. J Clin Oncol 14:1098-1105, 1996[Abstract/Free Full Text]

7. Bokemeyer C, Droz J-P, Hanauske A, et al: Treatment of relapsed nonseminomatous germ cell tumors with vinorelbine: A trial of the Phase I/II Study Group of the Association for Medical Oncology of the German Cancer Society. Onkologie 16:29-31, 1993

8. Puc HS, Bajorin DF, Bosl GJ, et al: Phase II trial of topotecan in patients with cisplatin-refractory germ cell tumors. Invest New Drugs 13:163-165, 1995[Medline]

9. Harstrick A, Schmoll H-J, Wilke H, et al: High-dose epidoxorubicin in refractory or relapsed nonseminomatous testicular cancer: A phase II study. Ann Oncol 2:375-376, 1990

10. Bokemeyer C, Beyer J, Metzner B, et al: Phase II study of paclitaxel in patients with relapsed or cisplatin-refractory testicular cancer. Ann Oncol 7:31-34, 1996[Abstract/Free Full Text]

11. Motzer RJ, Bajorin DF, Schwartz LH, et al: Phase II trial of paclitaxel shows antitumor activity in patients with previously treated germ cell tumors. J Clin Oncol 12:2277-2283, 1994[Abstract/Free Full Text]

12. Sandler AB, Cristou A, Fox S, et al: A phase II trial of paclitaxel in refractory germ cell tumors. Cancer 82:1381-1386, 1998[Medline]

13. Bokemeyer C, Hartmann JT, Kuczyk MA, et al: Recent strategies for the use of paclitaxel in the treatment of urological malignancies. World J Urol 16:155-162, 1998[Medline]

14. Motzer RJ, Bajorin DF, Bosl GJ, et al: Paclitaxel (T) containing first-line salvage therapy selected by risk for patients (pts) with germ cell tumors (GCT). Proc Am Soc Clin Oncol 16:322a, 1997 (abstr 1146)

15. Motzer RJ, Green GA, McCaffrey JA, et al: Paclitaxel (T), ifosfamide (I), and cisplatin (P) as first-line salvage therapy for relapsed germ cell tumor (GCT) patients with favorable prognostic features. Proc Am Soc Clin Oncol 17:322a, 1998 (abstr 1241)

16. De Wit R, Louwerens M, De Mulder PHM, et al: A dose finding study of paclitaxel (Taxol) added to fixed doses of bleomycin, etoposide, cisplatin (BEP) in patients with adverse prognosis germ cell cancer or carcinoma of unknown primary (CUP). Proc Am Soc Clin Oncol 17:322a, 1998 (abstract 1240)

17. Beyer J, Bokemeyer C, Rick O, et al: Salvage treatment in germ-cell tumors using Taxol, ifosfamide, cisplatin (TIP) followed by high-dose carboplatin, etoposide and thiotepa (HDCET): First results. Proc Am Soc Clin Oncol 17:322a, 1998 (abstract 1242)

18. Maas K, Daikeler T, Kanz L, et al: Activity of gemcitabine in platinum-resistant ovarian germ cell cancer. Eur J Cancer 32A:1437-1438, 1996

19. Plunkett W, Huang P, Xu YZ,et al: Gemcitabine: Metabolism, mechanisms of action, and self-potentiation. Semin Oncol 22:3-10, 1995[Medline]

20. Noble S, Goa KL: Gemcitabine: A review of its pharmacology and clinical potential in non-small cell lung cancer and pancreatic cancer. Drugs 54:447-472, 1997[Medline]

21. Stadler WM, Kuzel T, Roth B, et al: Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. J Clin Oncol 15:3394-3398, 1997[Abstract/Free Full Text]

22. Einhorn LH: Phase II trial of gemcitabine plus cisplatin in non-small cell lung cancer: A Hoosier Oncology Group study. Semin Oncol 24:S8:24-26, 1997

23. Gatzemeier U, Shepherd FA, Le Chevalier T, et al: Activity of gemcitabine in patients with non-small cell lung cancer: A multicentre, extended phase II study. Eur J Cancer 32A:243-248, 1996

24. Carmichael J, Possinger K, Philip P, et al: Advanced breast cancer: A phase II trial with gemcitabine. J Clin Oncol 13:2731-2736, 1995[Abstract]

25. Stender MJ, Loehrer PJ, Williams SD, et al: A phase II trial of gemcitabine in relapsed/refractory germ cell tumor (GCT). Proc Am Soc Clin Oncol 17:321a, 1998 (abstr 1238)

26. Huang P, Plunkett W: Induction of apoptosis by gemcitabine. Semin Oncol 22:19-25, 1995

Submitted June 24, 1998; accepted October 26, 1998.

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