Advertisement

International Journal of Clinical Oncology

, Volume 22, Issue 5, pp 857–864 | Cite as

Post-recurrence chemotherapy for mesothelioma patients undergoing extrapleural pneumonectomy

  • Teruhisa Takuwa
  • Masaki Hashimoto
  • Seiji Matsumoto
  • Nobuyuki Kondo
  • Kozo Kuribayash
  • Takashi Nakano
  • Seiki Hasegawa
Original Article

Abstract

Background

Additional chemotherapy is often not feasible in patients with recurrent malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP), due to deteriorated cardiopulmonary reserve. We thus examined the feasibility and efficacy of additional chemotherapy in patients with recurrent MPM after EPP.

Methods

A retrospective review was conducted of 59 consecutive patients who underwent bi-/tri-modal treatment with induction chemotherapy, EPP, and radiation therapy from July 2004 to August 2013 at Hyogo College of Medicine (Nishinomiya, Japan).

Results

Of 59 patients, 39 (male/female = 31/8, right/left = 15/24, pathological stage I/II/III/IV = 1/7/23/3, bi-/tri-modality = 27/12) relapsed at a median age of 62 (range 37–71) years. The median time to recurrence after EPP was 11.6 months. Of the 39 relapsed patients, 12 received best supportive care alone, six started but discontinued chemotherapy, and the remaining 21 (53%) completed more than three cycles of intravenous chemotherapy. The median survival time after EPP was significantly longer in 21 patients who received additional chemotherapy than in 18 patients who did not (39.2 vs. 12.2 months, P = 0.009).

Conclusions

Additional systemic chemotherapy was successfully administered in more than 50% of relapsed patients after bi-/tri-modal treatment, which included EPP, and resulted in a longer survival in comparison with best supportive care alone.

Keywords

Extrapleural pneumonectomy Malignant pleural mesothelioma Post-recurrence chemotherapy Radiation therapy Best supportive care 

Introduction

Extrapleural pneumonectomy (EPP) provides more adequate cytoreduction and surgical radicality than extended pleurectomy/decortication (P/D) [1]. However, some recent studies comparing EPP to P/D have questioned the survival benefit of EPP [2, 3, 4]. Of these, Rena et al. [5] reported that overall survival after EPP was lower than that after P/D. The reason why P/D is less radical is not apparent, although the low feasibility rate of additional chemotherapy for malignant pleural mesothelioma (MPM) recurrence after EPP has been proposed. Perrot et al. [6] and Jassem et al. [7] reported that, although chemotherapy regimens that included pemetrexed elicited a significant tumor response and delayed disease progression in recurrent MPM cases after EPP, only 25% of patients received additional chemotherapy, because of deteriorated cardiopulmonary reserve. Survival time after relapse is relatively short, at only 3 months [8]. This study aimed to retrospectively examine the feasibility and efficacy of additional chemotherapy for patients with recurrent MPM undergoing EPP.

Patients and methods

Study design

Medical records of patients with recurrent MPM undergoing EPP who were prospectively registered for bi-/tri-modal treatment, including EPP, from January 2004 to August 2013 at our institution were retrospectively reviewed. The procedures followed were in accordance with the institutional ethical standards of the responsible committee on human experimentation.

Eligibility criteria

Patients with histologically-proven MPM and potentially resectable stage disease (T1–3, N0–1, M0), with no major co-morbidity precluding chemotherapy, surgery, or hemithoracic radiation therapy, were eligible for multimodal treatment. Disease stage was routinely staged with chest and abdomen computed tomography and brain magnetic resonance imaging (MRI)/positron emission tomography (PET). All patients included in this study had an Eastern Cooperative Oncology Group performance status (PS) of 0–1 and were aged <75 years. Cardiac function was evaluated by electrocardiography and echocardiography. Pulmonary function tests and ventilation–perfusion scintigraphy were performed to assess respiratory reserve. Patients with a predicted post-EPP residual forced expiratory volume in 1 s of <1 L and those with sarcomatoid MPM were excluded.

Treatment schedule

  1. 1.

    Before 2006, the neoadjuvant chemotherapy regimen comprised cisplatin (40 mg/m2) plus CPT-11 (40 mg/m2) on days 1 and 8 and doxorubicin (30 mg/m2) on days 2 and 9. After 2007, the regimen was changed to pemetrexed (500 mg/m2) plus cisplatin (60–75 mg/m2) once every 21 days. EPP was performed 4–8 weeks after chemotherapy completion.

     
  2. 2.

    EPP included en bloc resection of the lung, parietal pleura, and, if needed, the ipsilateral diaphragm and ipsilateral pericardium. Previous biopsy sites were removed by limited chest wall resection. The diaphragm and pericardium were reconstructed using 2-mm Gore-Tex patches (GORE-TEX® Soft Tissue Patch 13150S; W.L. Gore & Associates, Inc., Newark, DE, USA) or, if required, 0.1-mm Gore-Tex patches (PRECLUDE® Pericardial membrane 1PCM102; W.L. Gore & Associates, Inc.).

     
  3. 3.

    Radiotherapy was usually started 8–12 weeks after EPP. Treatment fields included the ipsilateral hemithorax and mediastinum. Radiotherapy to the hemithorax was applied at 54 Gy.

     

Follow-up after multimodal treatment

After multimodal treatment, no additional treatment was performed before tumor recurrence. At every 2–3-month follow-up for MPM recurrence after multimodal treatment, outpatients underwent examinations, including blood sampling, chest X-ray, and chest/abdominal computed tomography or PET/computed tomography. Additional biopsies for cytological or histological examination of disease progression were performed as necessary, to document recurrent disease. All patients were followed up until death or June 2015.

Statistical analyses

Categorical variables were compared using the chi-squared test. Survival was calculated from the time of EPP until tumor recurrence. Kaplan–Meier curves were plotted and survival times between the two treatment arms were compared using the log-rank test. SPSS software (version 22; IBM-SPSS, Inc., Chicago, IL, USA) was used for all statistical analyses.

Results

Between January 2004 and August 2013, 59 consecutive patients with biopsy-proven MPM underwent multimodal treatment, which included EPP. Of these patients, there were two cases of perioperative death including one case of in-hospital death (post-operation day 48, acute respiratory distress syndrome) and one case of operation-related death (post-operation day 15, bleeding from aortic arch); 39 had recurrence. A retrospective data review of these 39 recurrent patients was performed in this study. The treatment schema is shown in Fig. 1.
Fig. 1

Between January 2004 and August 2013, 59 patients received multimodal treatment that included EPP and 39 patients developed recurrent disease. These 39 cases were retrospectively examined

Patient characteristics

The patient cohort included 31 males and eight females, with a median age of 62 (range 37–71) years. Of the 39 procedures performed, 15 were right-sided and 24 were left-sided. Patient characteristics and multimodal treatment variables in the 39 recurrent MPM patients are reported in Table 1.
Table 1

Comparison of patient characteristics and multimodal treatment variables

Factor

Total (N = 39)

CT group (N = 21)

No-CT group (N = 18)

P

Male/female

31/8

17/4

14/4

NS

Age, years (range)

62 (37–71)

62 (47–71)

64 (37–70)

NS

Right/left

15/24

8/13

7/11

NS

Neoadjuvant therapy (CDDP +PEM/others/without therapy)

29/7/3

14/4/3

15/3/0

NS

Radiological response using modified RECIST (PR/SD/PD/without therapy)

9/24/1/5

4/13/1/3

5/11/0/2

NS

Pathological stage (I/II/III/IV)

1/7/28/3

1/5/14/1

0/2/14/2

NS

Histological type (epithelioid/others)

35/4

20/1

15/3

NS

Adjuvant RT (±)

27/12

16/5

11/7

NS

EPP-related factors

 Surgical duration, min (range)

470 (332–769)

470 (332–667)

482 (347–769)

NS

 Blood loss, mL (range)

1340 (490–4530)

1340 (500–4425)

1460 (490–4530)

NS

 Period of hospital stay, days (range)

30 (17–122)

30 (17–44)

33 (21–122)

NS

 Adverse event (>G3/G3)

18/11

9/12

9/9

NS

RECIST response evaluation criteria in solid tumours, PR partial response, SD stable disease, PD progression disease, G Grade

  1. 1.

    Neoadjuvant chemotherapy

    Of the 39 patients, 36 (92%) completed three or more planned cycles of neoadjuvant chemotherapy: 29 (80%) completed three or more cycles of the prescribed cisplatin plus pemetrexed regimen and seven (20%) received cisplatin plus CPT-11 plus doxorubicin. The remaining two patients received no chemotherapy before EPP because of poor tolerance or patient refusal after one cycle completion.

     
  2. 2.

    EPP

    All 39 patients underwent EPP. The median postoperative in-hospital stay was 30 (range 17–122) days. The median surgical duration was 470 (range 332–769) min. Median blood loss volume was 1340 (range 490–4530) mL. A total of 18 (50%) patients developed complications greater than grade 3 according to ver. 4 of the Common Terminology Criteria for Adverse Events.

     
  3. 3.

    Pathological stage

    According to the International Mesothelioma Interest Group pathological staging system, one patient had Stage I disease, seven had Stage II, 28 had Stage III, and three had Stage IV. The histological type of mesothelioma was epithelioid in 36 patients, biphasic in two, and sarcomatoid in one.

     
  4. 4.

    Adjuvant radiotherapy

    After EPP, 27 (69%) patients received adjuvant hemithoracic radiotherapy at a dose of 54 Gy, while 12 (31%) received no radiotherapy because of bronchial fistula with emphysema (N = 3), continuous general fatigue (N = 3), or failure to thrive after hemithoracic radiotherapy using a regimen developed in our institution (N = 6).

     
  5. 5.

    Median time from EPP to recurrence was 11.6 (range 1.6–96) months.

     

Recurrence pattern

A total of 55 recurrent tumors were detected (local N = 41; distant N = 14). Disease recurrence was detected at more than one site in some patients. The sites of local recurrence comprised the ipsilateral chest wall (N = 19), abdominal cavity (N = 13), mediastinal and supraclavicular lymph nodes (N = 5), and pericardium (N = 4). Distant disease recurrence involved the contralateral lung in nine patients, and the bone, kidney, liver, and brain in one patient each. Of 14 cases of distant recurrence, six were accompanied by local recurrence.

Additional chemotherapy for post-EPP recurrence

The schema for management of recurrent disease is shown in Fig. 2. All 39 patients chose to undergo additional chemotherapy at the time of recurrence, although treatment was contraindicated for 12 patients because of inadequate PS, such as general fatigue and appetite loss. In addition, six patients started chemotherapy, but were unable to complete the regimen. Thus, these 18 patients (46%) received incomplete or no additional chemotherapy and were assigned to the No-CT group, while 21 (54%) patients completed more than three cycles of intravenous additional chemotherapy after diagnosis of recurrence and were assigned to the CT group.
Fig. 2

Treatment strategy for post-EPP recurrence and outcome. PS performance status, CT chemotherapy

Regimen and cycles

Of the 21 patients in the CT group, as a first-line treatment against MPM recurrence, 14 received more than three cycles of pemetrexed (500 mg/m2) plus cisplatin (60–75 mg/m2) or carboplatin AUC 5 (area under the concentration vs. time curve) once every 21 days, three received more than four cycles of gemcitabine (1000 mg/m2) plus CPT-11, and two received more than three cycles of single agent pemetrexed (500 mg/m2) once every 21 days. Two patients received other regimens (one received four cycles of carboplatin plus vinorelbine and the other received seven cycles of cisplatin plus CPT-11 plus doxorubicin). As a second-line treatment for disease progression after first-line treatment, eight patients received several cycles of single-agent pemetrexed (500 mg/m2) and four received gemcitabine plus CPT-11 or single-agent gemcitabine alone. All 21 patients in the CT group completed more than three cycles of intravenous chemotherapy and most received multiple chemotherapies (Fig. 3).
Fig. 3

CT group patients (n = 21) completed more than three cycles of intravenous chemotherapy and most received multiple-line chemotherapies. GEM gemcitabine, CPT-11 camptothecin-11, PEM pemetrexed, CDDP cisplatin

CT group and No-CT group

As shown by the comparison of patient characteristics and multimodal treatment variables presented in Table 1, there were no statistically significant differences in patient sex and age, pathological stage, histological type, or multimodal treatment variables between the CT and No-CT groups (also see Table 1).

Survival

The overall median survival time (MST) after EPP of all cases (N = 39) was 22.0 [95% confidence interval (CI) = 13.8–30.2] months and the one- and two-year survival rates were 69.2 and 41.0%, respectively (Fig. 4). The MST after recurrence was 6.5 (95% CI = 1.7–11.2) months and the one- and two-year survival rates were 40.0 and 20.0%, respectively.
Fig. 4

Kaplan–Meier overall survival from EPP of all cases (N = 39). The median survival time was 22.0 (95% CI = 13.8–30.2) months. The 1- and 2-year survival rates were 69.2 and 41.0%, respectively

The MST and 1-, 2-, and 5-year survival rates after EPP were significantly longer for the CT group that the No-CT group (39.2 vs. 12.2 months, 85.7 vs. 50.0%, 49 vs. 18.2%, and 31.0 vs. 5.6%, respectively, P = 0.009, Fig. 5). MST after recurrence was also significantly longer in the CT group than the No-CT group (12.8 vs. 3.1 months; 95% CI = 2.5–23.0 and 1.8–4.4 months, respectively, P = 0.006). Likewise, median disease-free survival was significantly longer in the CT group than the No-CT group (19.8 vs. 5.7 months, 95% CI = 16.0–23.7 vs. 1.8–9.7 months, respectively, P = 0.02). The median follow-up period after EPP for this cohort was 22.0 (range 3.0–102) months (Table 2).
Fig. 5

Overall survival according to the completeness of chemotherapy after recurrence (comparison between the CT and No-CT groups, P = 0.009). The median survival of the CT group was 39.2 months (n = 21). The median survival of the No-CT group was 12.2 months. The 1-, 2-, and 5-year survival rates of the CT/No-CT groups were 85.7/50.0, 49/18.2, and 31.0/5.6%, respectively

Table 2

Comparison of median survival time after EPP and recurrence

Factor

Total (N = 39)

CT group (N = 21)

No-CT group (N = 18)

P

Time to recurrence after EPP, months (range)

11.6 (1.6–96)

19.8 (16–23.7)

5.7 (1.8–9.7)

0.02

MST after EPP, months (range)

22.0 (13.8–30.2)

39.2 (32.8–45.5)

12.2 (9.9–14.4)

0.009

MST after recurrence, months (range)

6.5 (1.7–11.2)

12.8 (2.5–23.0)

3.1 (1.8–4.4)

0.006

Discussion

Two types of surgery are recommended for MPM: EPP and P/D. P/D is a lung-sparing surgery, in which the parietal and visceral pleura, and, if needed, the diaphragm and pericardium, are resected. Although both surgeries are cytoreductive, the residual tumor is smaller following EPP than P/D, as expected, since EPP is theoretically more radical [9]. However, several recent reports concluded that EPP offered less survival benefit than P/D in the context of multimodal therapy. A meta-analysis conducted by Cao et al. [3] concluded that P/D was associated with lower perioperative morbidity and mortality rates with similar, if not superior, long-term survival, compared to EPP. Our speculation for the lower survival benefit of EPP is the higher perioperative mortality rate of up to 12.5% with EPP [10, 11]. Moreover, EPP presents a greater risk of deterioration of postoperative cardiopulmonary function and is associated with lower tolerance to chemotherapy in case of recurrence. Patients undergoing EPP have poorer tolerance to diseases other than MPM, such as pneumonia and heart failure.

Because of the deterioration of postoperative cardiopulmonary function after EPP, the prognosis of patients with recurrent MPM undergoing EPP is reportedly poor, because only a few subsequent therapeutic options are available. In a single-center study of 16 patients who developed recurrence after multimodal therapy, including EPP, Perrot et al. [6] reported that only four received additional chemotherapy after detection of recurrence. Baldini et al. [8] reported that 21 of 25 patients who developed recurrence after EPP died at a median time of three (range 0–24) months from time of relapse. In contrast, some additional chemotherapy regimens are available after P/D. Bolukbas et al. [12] reported that PS was still good in some patients undergoing P/D at the time that MPM recurrence was detected, which allowed for a full dose of second-line and third-line therapies. In their study, 18 (54%) of 33 patients were eligible for further therapy options [12].

The recurrence rate after surgery is high because both procedures are cytoreductive. Gomez et al. [13] reported local recurrence in 16% (14/87) of patients and distant metastasis in 59% (51/87) after EPP. Baldini et al. [8] also reported a relatively high rate of recurrent disease of 75% after EPP. Consistent with these reports, recurrent disease was detected in 66% of patients included in the present study. To improve the prognosis of MPM, it is important to choose an effective additional treatment at the time of relapse.

Several reports have concluded that chemotherapy appears to be an effective and feasible option to improve survival and suppress tumor progression. Vogelzang et al. [14] reported in their multicenter, randomized phase III study that treatment with pemetrexed plus cisplatin resulted in significantly improved MST in MPM patients, compared with treatment with cisplatin alone (12.1 vs. 9.3 months, respectively, P = 0.02). This trial also demonstrated that combination chemotherapy was well tolerated, time to disease progression was significantly longer, and response rates were significantly higher. Moreover, a phase III trial conducted by Manegold et al. [15] demonstrated that second-line chemotherapy for the management of MPM was associated with significantly prolonged survival. Jassem et al. [7] also found that second-line pemetrexed elicited a significant tumor response and delayed disease progression in a phase III study. However, to date, very few studies have investigated the effect of additional chemotherapy against progression of recurrent MPM after multimodal treatment that included EPP. Also, at present, there is no consensus on a standard treatment schema, and thus management is planned on a patient-by-patient basis.

Gerbaudo et al. [16] reported that patients who received additional chemotherapy after multimodal treatment for relapsed MPM achieved longer survival than those who received no additional treatment (N = 12 and 30; median survival, 13 vs. 6 months, respectively), although this result was not statistically significant (P = 0.26). Kostron et al. [17] reported recently that 74% of patients were treated for recurrent MPM with second-line additional therapy after tumor relapse and survived significantly longer than those who received no additional therapy (P < 0.0005). In contrast to these past reports that additional chemotherapy for recurrence MPM after EPP is often considered impossible, a relatively large number of relapsed patients in our cohort who underwent chemotherapy after disease recurrence achieved relatively good treatment outcomes.

At our institution, disease relapse is initially treated with chemotherapy; thereafter, some patients with localized recurrence undergo surgical resection or radiotherapy, depending on the characteristics of the lesion and the condition of the patient.

As a unique finding contrasting with those of past studies, our analysis revealed that 54%, a relatively large portion, of relapsed patients were suitable for chemotherapy and patients in the CT group achieved a greater MST than those in the No-CT group (12.8 vs. 3.1 months, respectively). Our data showed an remarkable long-term outcome benefit of additional chemotherapy after recurrence. Hence, additional chemotherapy for recurrence of MPM after EPP appears feasible and should be considered.

The speculative reason for the high chemotherapy implementation rate after recurrence and good survival data in our CT cohort is that patients undergoing additional chemotherapy maintained good PS and physical condition after EPP, and early diagnosis of recurrent MPM is essential because additional treatment must be started before widespread metastasis occurs. Our short follow-up interval and modalities may have contributed to the early diagnosis of asymptomatic recurrent MPM among patients with good PS.

We conclude that additional chemotherapy after EPP recurrence might be both feasible and effective. However, the absolute efficacy of additional chemotherapy might not be accurately derived from our results because of the retrospective nature of the data set and patient selection bias. Secondly, patients sufficiently fit to undergo additional chemotherapy might have had tumors with low biological malignancy and slow or minimal relapse patterns, as MPM is a biologically diverse disease, which might explain the various patterns of recurrence. Thirdly, the final criteria for the indication of chemotherapy are incomplete and often decided on a patient-by-patient basis, although all recurrent patients were scheduled to receive additional chemotherapy. We also should assess the feasibility rate of additional chemotherapy for MPM recurrence after EPP compared with that after P/D in the future.

Finally, patients unfit for additional chemotherapy had widespread metastasis of disease or poor PS at recurrence. Early diagnosis in accordance with strict follow-up criteria and early administration of additional chemotherapy are important to improve recurrent MPM prognosis.

Notes

Acknowledgements

The authors would like to thank Enago (www.enago.jp) for the English language review.

Compliance with ethical standards

Funding

None declared.

Conflict of interest

All authors have declared no conflicts of interest.

References

  1. 1.
    Rice D, Rusch V, Pass H et al. (2011) Recommendations for uniform definitions of surgical techniques for malignant pleural mesothelioma: a consensus report of the international association for the study of lung cancer international staging committee and the international mesothelioma interest group. J Thorac Oncol 6(8):1304–1312. doi: 10.1097/JTO.0b013e3182208e3f CrossRefPubMedGoogle Scholar
  2. 2.
    Lang-Lazdunski L, Bille A, Lal R et al. (2012) Pleurectomy/decortication is superior to extrapleural pneumonectomy in the multimodality management of patients with malignant pleural mesothelioma. J Thorac Oncol 7(4):737–743. doi: 10.1097/JTO.0b013e31824ab6c5 CrossRefPubMedGoogle Scholar
  3. 3.
    Cao C, Tian D, Park J et al. (2014) A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer 83(2):240–245. doi: 10.1016/j.lungcan.2013.11.026 CrossRefPubMedGoogle Scholar
  4. 4.
    Lang-Lazdunski L (2014) Surgery for malignant pleural mesothelioma: why, when and what? Lung Cancer 84(2):103–109. doi: 10.1016/j.lungcan.2014.01.021 CrossRefPubMedGoogle Scholar
  5. 5.
    Rena O, Casadio C (2012) Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: an harmful procedure. Lung Cancer. doi: 10.1016/j.lungcan.2011.12.009 Google Scholar
  6. 6.
    de Perrot M, Feld R, Cho BC et al. (2009) Trimodality therapy with induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Clin Oncol 27(9):1413–1418. doi: 10.1200/JCO.2008.17.5604 CrossRefPubMedGoogle Scholar
  7. 7.
    Jassem J, Ramlau R, Santoro A et al. (2008) Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol 26(10):1698–1704. doi: 10.1200/jco.2006.09.9887 CrossRefPubMedGoogle Scholar
  8. 8.
    Baldini EH, Recht A, Strauss GM et al. (1997) Patterns of failure after trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 63(2):334–338CrossRefPubMedGoogle Scholar
  9. 9.
    Hasegawa S (2014) Extrapleural pneumonectomy or pleurectomy/decortication for malignant pleural mesothelioma. Gen Thorac Cardiovasc Surg. doi: 10.1007/s11748-014-0389-7 PubMedPubMedCentralGoogle Scholar
  10. 10.
    Treasure T, Lang-Lazdunski L, Waller D et al. (2011) Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol 12(8):763–772. doi: 10.1016/s1470-2045(11)70149-8 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hasegawa S, Okada M, Tanaka F et al. (2015) Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial). Int J Clin Oncol. doi: 10.1007/s10147-015-0925-1 Google Scholar
  12. 12.
    Bolukbas S, Manegold C, Eberlein M et al. (2011) Survival after trimodality therapy for malignant pleural mesothelioma: radical pleurectomy, chemotherapy with cisplatin/pemetrexed and radiotherapy. Lung Cancer 71(1):75–81. doi: 10.1016/j.lungcan.2009.08.019 CrossRefPubMedGoogle Scholar
  13. 13.
    Gomez DR, Hong DS, Allen PK et al. (2013) Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma. J Thorac Oncol 8(2):238–245. doi: 10.1097/JTO.0b013e31827740f0 CrossRefPubMedGoogle Scholar
  14. 14.
    Vogelzang NJ, Rusthoven JJ, Symanowski J et al. (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21(14):2636–2644. doi: 10.1200/JCO.2003.11.136 CrossRefPubMedGoogle Scholar
  15. 15.
    Manegold C, Symanowski J, Gatzemeier U et al. (2005) Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma. Ann Oncol 16(6):923–927. doi: 10.1093/annonc/mdi187 CrossRefPubMedGoogle Scholar
  16. 16.
    Gerbaudo VH, Mamede M, Trotman-Dickenson B et al. (2011) FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival. Eur J Nucl Med Mol Imaging 38(5):810–821. doi: 10.1007/s00259-010-1704-x CrossRefPubMedGoogle Scholar
  17. 17.
    Kostron A, Friess M, Crameri O et al. (2015) Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesotheliomadagger. Eur J Cardiothorac Surg. doi: 10.1093/ejcts/ezv398 Google Scholar

Copyright information

© Japan Society of Clinical Oncology 2017

Authors and Affiliations

  • Teruhisa Takuwa
    • 1
  • Masaki Hashimoto
    • 1
  • Seiji Matsumoto
    • 1
  • Nobuyuki Kondo
    • 1
  • Kozo Kuribayash
    • 2
  • Takashi Nakano
    • 2
  • Seiki Hasegawa
    • 1
  1. 1.Department of Thoracic SurgeryHyogo College of MedicineNishinomiyaJapan
  2. 2.Department of Respiratory MedicineHyogo College of MedicineNishinomiyaJapan

Personalised recommendations